2Objectives Discuss lab values related to anemia management >Interpret CBC results, including H/H, RDW (red celldistribution width), MCV (mean corpuscularvolume) and MCHC (mean corpuscular hemoglobinconcentration)>Examine iron study results, focusing on ironsaturation and ferritin
3ObjectivesDiscuss the complex relationship between calcium, phosphorus, vitamin D and PTH>Review bone and mineral pathophysiology>Discuss why interventions involve thinking about allfour of the above lab values>Outline when lab values are “only” abnormal vs whenthey are alarming>Discuss treatment of bone and mineral abnormalitieswith medications and surgery
4ObjectivesDiscuss how dialysis adequacy is determined and used in a clinical setting>Discuss URR, Kt/V and PET, how to calculate thesemeasures and how to interpret the results>Discuss the advantages and disadvantages of URR(Urea Reduction Ratio) vs Kt/V>Examine when, why and how the dialysis prescriptionshould be adjusted
5Plan Briefly present basic information for each topic Hopefully, present new information for each topicCase studies will help to enhance understanding of information presented
6AnemiaAnemia is defined as a decrease in red blood cells (RBC’s)
7Anemia Decrease in RBC’s can be due to a variety of factors….. >Abnormal destruction of red blood cells (e.g.hemolytic anemia, sickle cell disease)>Lack/decreased cell production from bone marrow(e.g. aplastic anemia, myeloproliferative disorders)>Blood loss (e.g. GI Bleed)>Lack of substances needed to produced RBC’s>All of the above seen in people with CKDMyeloproliferative disorders is the name for a group of conditions that cause blood cells -- platelets, white blood cells, and red blood cells -- to grow abnormally in the bone marrow.
8Substances Needed for RBC Formation NECESSARY SUBSTANCE/STRUCTURERELATED INFORMATIONErythropoietin (hormone)Stimulates bone marrow to produce RBC’sNeed adequate nutrients—e.g. Iron, Vitamin B12, Folic acidTo produce hemoglobinDNAChronic inflammation 2/2 infection and/or autoimmune disorders (e.g. Lupus) impairs DNA synthesis => anemiaBone marrowImages fromReticulocyte count reflects ability of bone marrow to produce RBC’s. Retic ulocyte = immature RBC’sAnemia in ESRD, can see decreased RBC production (lack of substances to make cells) and increased retic count.A very elevated retic count points to increase RBC destruction or hemolysis as a potential cause of anemia.
9Anemia Management Current practice >If Hgb less than 10 g/dl x 2, start Epogen/Aranesp>Hgb levels checked at least monthly (KDOQI)>Goal: maintain Hgb between 10 and 12 g/dl>CREATE and CHOIR study>Do not know optimal Hgb for people with CKD>If Hgb exceeds upper limit (12 g/dl) or increases more than 1 g/dl in2 wks:>Hold the dose (per FDA)>No benefits to hemoglobin > 13 g/dl. In fact, increasesthe risk of clots, vascular events (heart attack and stroke) anddeath
10Anemia Management “New?” >TREAT--Trial to Reduce Cardiovascular Events withAranesp Therapy (people not on dialysis)>Study completed in 2009>Recommends Hgb >10 and <11 g/dl>Reduce risk of clots, heart attacks, stroke and death>Several other studies currently underway>Will guidelines for people on dialysis also change?
11Anemia Let’s define lab values reported in a CBC results: >Red blood cells>Hemoglobin>Hematocrit>Reticulocyte count>MCV (mean corpuscular volume)>MCHC (mean corpuscular hemoglobinconcentration)>RDW (red cell distribution width)
12Red Blood Cells and Hemoglobin Red blood cells (RBC)>Normal life span 120 days/80-90 days if on dialysis>Decreased life span due to toxic, uremic environment*>Composed of mostly water and hemoglobinHemoglobin>Hgb molecule made of iron and protein>The predominantprotein in RBC>Carries oxygen*Ly, et al (200$)
13Hemoglobin CKD abnormal H/H; what are critical Hgb values? Hgb values below 5 g/dl can cause heart failureHgb values above 13 g/dl can cause CV events/death*KDOQI Anemia Guidelines: 2007 Update
14Hematocrit Hematocrit >% of RBC in plasma (liquid part of the blood)>Increase/decrease of plasma volume affects thehematocrit values>Decrease occurs with over hydration (diluted)>Increase occurs with under hydration(concentrated blood volume)>How would Hct change before/after dialysis?>What lab value used to dose epo? Why?>If RBC and Hgb are normal, estimate Hct bymultiplying the Hgb times 3. (10 x 3 = 36)
15Reticulocyte CountReticulocytes are immature forms of erythrocytes (also called RBC’s)>Up to 1.5% “normal” in men>Up to 2.5% “normal” in women>Low retic count seen with folic acid deficiency>High retic count seen when the bone marrow is respondingto an increase need for RBC’s. Bone marrow can’t produceenough mature RBC’s fast enough, so it does the nextbest “thing”, increases the production of immature RBC’s>What would you expect a retic count to be in a person withESRD on dialysis?
16RDW (RBC Distribution Width) >Indicator of variation in the size of red blood cells>Values > 14.5% = RBC vary a lot in size>Immature red cells usually larger>RDW increased in those with ESRDWhy?Bone marrow working hard to produce enoughred blood cells but can’t produce enough maturecells to keep up with demand.
17MCV and MCHC Results MCV (mean corpuscular volume) >Measures average size of RBCMCHC (mean corpuscular hemoglobin concentration)>Measures % of hemoglobin in the RBC>Hgb/Hct x 100Why should I care about the MCV and MCHC values?
18What the MCV and MCHC Tells You TestNormal RangeValue Below Range(Microcytic = small than normal)Value Above Range(Macrocytic = larger than normal)Value Within RangeMCV(mean corpuscular volume)(size of RBC)femoliters< 80 =Iron deficiency anemia, congenital anemias> 100 =Folic acid deficiency, B12 deficiency, myelodysplastic, leukemias=Anemia due to blood loss or a chronic diseaseMCHC(mean corpuscular hemoglobin concentration) (% RBC in fluid)32-35%< 32% =Iron deficiency anemia> 35% = same as above32-35% =
19AnemiaCase study>E.R. is a 39 y/o Hispanic female. Separated with 3children, ages 12, 13 and 19 years old.>ESRD of unknown etiology; transplant in 2003.Kidney was from her sister.>Rejection (per renal biopsy) August 2010;restarted dialysis in August 2010.>Receives dialysis via ED every 4-5 days.>Receives Aranesp every 2-3 weeks with dialysis.
20Putting It All Together Before looking at lab values, you should be asking….>What are normal vs. abnormal values?>What information does the abnormal lab values“tell” you?>Are there any alarming/critical lab values?
24Measuring Iron Where iron is found Two tests used to estimate iron stores: Ferritin and Saturation>Ferritin>Is a protein that binds to iron; helps to transport iron in the body>Most ferritin is found in the liver, spleen, muscle and bone marrowwith a small amount found in the blood>Normally, 1 ng of ferritin (in blood) = 10 ng of iron stores (in liver, spleen, muscle and bonemarrow)>Ferritin is a proxy measure for iron stores and has it ‘s limitations.Image retrieved August 11, 2011 from
25Ferritin Low ferritin levels usually indicates iron deficiency High ferritin levels, however…..>Does not necessarily indicate adequate iron stores>Many factors can increase ferritin levels, e.g. recent iron infusion, infection,inflammation, e.g. autoimmune disorders, malignancy, blood transfusions(250 mg of iron/1 unit packed red cells)>Wait two weeks before measuring iron stores after giving iron load (morethan 125 mg/week)>Can become iron toxic (ferritin greater than 1000)>High levels can be due to inherited disorders or too much ironadministration>Toxic levels of iron can cause organ failure and death
26DRIVE STUDYDialysis Patients’ Response to IV iron with elevated ferritin Study (DRIVE)>Provided some clarification for safe upper limits offerritin levels in hemodialysis patients.>Ferric gluconate (ferrlecit) administration is superiorto no iron therapy in anemic dialysis patientsreceiving epogen and ferritin levels of 500 to 1200ng/ml and Tsats of <or=25%.Retrieved August 11, 2011 from
27Iron Saturation Complete name = transferrin iron saturation or Tsat >Estimates ability to bind iron andtransport it to various sites in thebody>Serum iron / total iron bindingcapacity X 100More sensitive than ferritin; not affected by inflammation/infection
28Goal for Iron Stores* HD-CKD ND-CKD/PD-CKD* Ferritin > 200 ng/ml Sats > 20%Ferritin > 100 ng/mlFrom KDOQI Anemia Guidelines*No RCT to support recommendation
29Iron Deficiency Many causes… >Blood loss >Celiac disease (decreases absorption of iron)>Hemolysis (RBC breaks apart)>Gastric bypass (decreases absorption)>Epogen administration, etc.Must identify cause of iron deficiency beforetreating
30Look at Entire PictureDecreasing ferritin/stable sats/decreasing Hgb = iron deficit>? external iron loss>Need more ironDecreasing ferritin and increasing Hgb = iron moving from storage to hemoglobin (e.g. in response to epogen administration)Increasing ferritin and decreasing sats and decreasing Hgb = inflammation>Increase ESA dose
31Case StudyCase Study>F.L. 86 yo female who attends the anemia/CKD clinic.History significant for….>HTN>CKD IV>Anemia>Unable to tolerate po iron supplements due to GIupset
32Case Study TEST/ INTERVENTION DATE = 11/8/2010 DATE = 12/22/2010 Hemoglobin8.8 (decreasing)7.79.5Hematocrit28.425.330.9Saturationnone10%Ferritin33BUN54 (increasing)5539Creatinine2.4 (increasing)2.352.04GFR23 ml/min24 ml/min28 ml/minAranesp doseIncreased to 200 mcg200 mcg
33Take Home Points for Anemia and Iron Administration Look at hemoglobin trends>If Hgb is decreasing>Don’t miss other causes of anemia>Increase epogenLook at iron sats and ferritin>If iron sats and ferritin both low, give iron>Remember iron is stored in places we don’t measure,so look at the entire clinical picture
34Bone and Mineral Balance Briefly discuss the four primary “players”:>Vitamin D>Calcium>Phosphorus>PTHDiscuss the complex interdependence amongst calcium, phosphorus, vitamin D and PTH
35Vitamin D2-3 Vitamin D comes from sun, food and our body 25-hydroxyvitamin D2produced in the liverNormally kidneys produce an enyzme that converts D2 to D3 (1,25 dihydroxyvitamin= calcitriol)
36Vitamin D A complex group of fat-soluble substances (D1-D5) >D2 = ergocalfciferol>Sources>Food—only found in seafood, mushrooms, eggyolks and fortified foods>OTC: Generic Vitamin D>Prescription: Drisdoll>Changed in the liver to 25-hydroxycholecalciferol (25-OH)>Measured in those with CKD Stages 3-5>25-OH changed in normal kidneys to 1,25dihydroxycholecalciferol>Measured in those with CKD Stage 3-6
37Vitamin D3 D3 = cholecalciferol >D3 = 1,25 dihydroxycholecalciferol >Decreased amounts produced in CKD>Also referred to as active Vitamin D>Sources: Calcitriol (Rocaltrol)Hectoral (doxercalciferol)Zemplar (paricalcitrol)Sunlight (converted to Vitamin D3 inthe skin)
38Vitamin D Lab ranges >25OH = < 30/32 >1,25 = 18-78 >Controversy on what level is normal & too highWhat does Vitamin D do?>Helps maintain serum calcium and phosphoruslevels/regulates release of calcium and phosphorusfrom the bone>Increases calcium absorption from the intestines>Suppresses PTH synthesis
39Calcium Functions >Maintains bone structure >Plays a major role in nerve conduction>Assists with muscle contraction/relaxationMost calcium found in boneSerum calcium binds to albumin>Serum calcium = Albumin = 2.5>0.8 x ( ) = 7.7>Corrected serum calcium more accurate>Corrected total calcium 8.4 to 9.5 mg/dl
40Hypercalcemia Long term consequences for those with CKD >Increased risk CV calcifications (larger arteries)>Calciphylaxis (soft tissue)Serum calcium > 13.0Causes>Medications (calcium acetate, zemplar)S/S of hypercalcemia>Depression, anxiety, muscle weakness, cognitivedysfunction, fatigue, hypertension, constipation>ECG changes/arrhythmias
42Hypocalcemia Causes >CKD (usually CKD Stages 5 & 6) >Medications (e.g. Cinacalcet, Hectoral)>Rapid correction of acidemia (CO2 low) duringhemodialysis can trigger tetany and seizures>”Hungry Bone Syndrome” after parathyroidectomy>Severe decrease in serum calcium due to abruptdecreased in PTH release; change upsets balanceof calcium moving to and from the bones
43Phosphorus 85% of phosphorus is found in bone and teeth Has many functions>Helps maintain health bone and teeth>Essential for storage of energy (ATP)>Helps maintain tissues, cells, DNA, and RNAPhosphate = 3.5 to 5.5 mg/dl
44Hyperphosphatemia Serum levels greater than 12 May be asymptomatic Signs and symptoms, if present>Pruritus, rash, bone and joint pain
45Elevated PhosphorusWhat is the role of dietary restriction in decreasing serum phosphorus levels?>Much phosphorus is found in high quality proteinfoods>Need high protein intake to prevent muscle wastingbut can limit dairy, some vegetables, processed foods and colas>Goal protein intake = 1 gm protein per kg of bodyweight per day
46Phosphorus and Protein 70 kg person = 70 gms protBreakfast>Two eggs>Two pieces toastLunch>Grilled chicken-4 oz>Garden salad-2 cupsDinner>Steak-4oz>Green beans-1cup>Apple-medium, fresh*www.davita.comFOODPHOS*PROTEIN*Eggs170 mg12 gmsBread60 mg4 gmsChicken265 mg36 gmsGarden Salad340 mg2 gmsSteak32 gmsGr. Beans25 mg1 gmsApple40 mg0 gms1355 mg88 gms
47Calculating Phosphorus Balance Intake = 1000 mg per day X 7 days = 7000 mg per weekGI tract absorbs 60% of what is consumed>7000 mg X 0.6 = 4200 mg phosphorus/wk800 mg eliminated/HD treatment = 2400 mg/wk4200 – 2400 = 1800 mgNet + phosphorus balance 1800 mg per week>1 Renagel binds about 100 mg phosphorus1 pill/meal X 100 = 300 x 7 days = 2100 mg/wk1800 mg – 2100 mg = 300 mg negative balance/wk
48Hypophosphatemia Serum levels less than 2.5 May be asymptomatic Causes >Not eating =>> malnutritionSymptoms, when present>Muscle weakness (e.g. diplopia, dysphagia)>Ventricular arrhythmias>Neuro manifestions (e.g. confusion, coma, seizures)>Poor oxygenation (phosphorus and ATP)
49Changes During Progression of CKD Kidneys’ excretion of phosphorus decreases, causing the serum phosphorus to increaseKidney does not reabsorb calcium and vitamin D is not activated, causing decreased serum calcium levelsVitamin D is not activated, causing parathyroid gland hypertrophy and hyperplasia>Decreased serum calcium and increased serumphosphorus levels caused increased secretion of PTH
50Changes During Progression of CKD Kidney dysfunction results in>Calcitriol (Vitamin D) deficiency>Hyperphosphatemia –kidneys no longer excrete phosphate>Decreased Vitamin D and increased phosphorus causeshypocalcemiaMajor factors responsible for stimulating PTH are>Hypocalcemia (sensed by receptors on parathyroid gland =>increased secretion of PTH)>Decreased vitamin D levels (1,25 dihydroxyvitamin D= calcitriol)>Hyperphosphatemia
51Bone and Mineral Balance Complex interdependence of calcium, phosphorus, vitamin D and PTH
53Treatment Goals – CKD VI Values Per KDOQI for CKD VIPTH = 150 to 300 pg/ml (PTH values vary with CKD stage)>Optimal PTH levels in advanced kidney disease notknownPhosphate = 3.5 to 5.5 mg/dlCorrected total calcium 8.4 to 9.5 mg/dlCalcium-phosphate product < 55 mg2/dl2>Larger doses Vitamin D analogs associated with increasedcalcium and phosphorusOutcomes>Manage secondary hyperparathyroidism>Manage calcium/phos/vitamin D abnormalities>Minimize vascular calcification
54Case StudyS.M., an 89 yo with HTN, DM, CVA (residual left sided weakness), MVR , CABG and CKD V>Very knowledge about dietary content for potassium andphosphorus>Medications>Coreg, Lotrel, Lasix, Mirtazapine, ASA, MVI,Vitamin D 1000 u/day, calcium acetate 667 mg/meal>Pleasant, alert and oriented>BUN 107, Creatinine 7.48, GFR 6 ml/min, K 4.8, CO2Decision made to start dialysis
55Lab Values for S. M. LAB TEST/DATE RESULT LAB RANGE Calcium/7.18.2011 8.7Corrected total calcium 8.4 to 9.5 mg/dlAlbumin3.5Corrected = 9.1Phosphorus/6.23.5 to 5.5 mg/dlVitamin D/25 OH 43.01,25 OH 17.025OH >30/321,23 = 18-78PTH/327150 to 300 pg/ml
56Take Home Points for BMD Must look at all lab values-calcium, albumin, phosphorus, vitamin D and PTH-to decide if any actions are neededWhile can “shoot” for stated lab values, getting all labsvalues within stated goal range can be very difficultMust always consider how the person feels/looks when interpreting lab results
57Dialysis AdequacyUsed to determine if enough dialysis is being delivered or if blood being “cleaned” enough?Adequate dialysis treatments “replace” less than 15% of normal kidney function/”adequacy” is relative term>Intermittent dialysis (3x per week) inefficient, onlydialyzing out toxins about 7% of the time while thebody produces toxins 100% of the time
58More About AdequacyUrea is not the only toxin, yet it is the one we measure>Urea = being water soluble, it is easily measuredHowever, there are 90 different compounds that are toxins that we don’t measure. Many of these compounds are more toxic than urea.>No current measure of adequacy for these different toxinsConventional dialysis has its limitations:>It removes urea (small, water soluble molecules)>Weekly clearance of urea = about 1/6th of normal physiologicclearance (what would be cleared by healthy kidneys)>28% of toxins are protein bound and not easily removedby dialysisYavuz, et al (2005)
59Dialysis AdequacyAdequacy is important since under-dialysis can cause:>Weakness and fatigue>Weight (muscle) loss> Nausea, decreased appetite> Sleep disturbances
60How Is Adequacy Determine? Three methods used to calculate adequacy:>URR = Urea Reduction Ratio (HD)>Kt/V (HD and PD)>PET = Peritoneal Equilibration Test (PD)
61URR (Urea Reduction Ratio) URR is one measure of how effectively a hemodialysis treatment has removed urea from the bloodFormula: preBUN – postBUN X 100 =preBUN94 (pre) – 32 (post) / 94 (pre) x 100 = 65.9% URR
62URR (Urea Reduction Ratio) No one percentage (URR) represents adequate dialysis. However, people usually live longer and have fewer hospitalizations if URR >= 60%>So, if no one number determines adequate dialysis,how does one choose a URR goal?Usually measured once per month
63Kt/VAlso measures how much urea is removed during dialysis, but takes into account two additional factors:>Urea made by the body during dialysis>Urea removed during dialysis along with excess fluidGoals* (many different values found in literature)>For CAPD, Kt/V = 2.0>Kt/V = 1.7 is minimal dose>For HD (adults and peds), Kt/V = 1.2 is minimal dose>As little as 3% residual renal function can increase theKt/V calculation from 1.2 to 1.65*KDOQI
64Kt/V SYMBOL EXPLANATION K Rate at which blood passes through the dialyzer in ml/mintTime (expressed in minutes)KtVolume of blood cleared of urea during one dialysis treatmentVVolume of water in a person’s body
65Calculating Kt/V* Example >Dialyzer’s clearance = 400 ml/min >Treatment time = 210 min (3.5 hours)>Kt = 400 ml/min x 210 min = 84,000 ml (84 L)>V = volume>Weight = 70 kg. 60% body water (average)>70 kg. x .60 = 42>Kt/V = 84/42 = 2.0>Would you/could you make any dialysis changes?*http://kidney.niddk.nih.gov/kudiseases/pubs/hemodialys is dose
66Changing the Kt/V Kt/V of 2.0 is too much >1.2 (goal)/2.0 (achieved) = 0.6> = 2.9 hours (decrease from 3.5 hours)Increasing the t (time)>if the Kt/V is 0.9 but the goal is 1.2:1.2/0.9 = 1.33 or 1.33 times more Kt needed3 hours (current) x 1.33 = 4 hours
67Difference Between URR and Kt/V Kt/V is more accurate then URR>URR measures urea removed during dialysis>Kt/V adds the amount of urea removed with excessfluidMore weight loss during dialysis will yield a higher Kt/V for the same URRURR may be lower than usual if large volume removedKt/V of 1.2 ~ URR 63%
68How Can Clearance of Toxins Be Increased? For both Kt/V and URR….>Increased the blood flow (Qb)>Increase treatment time>Use a larger dialyzer>Increased dialysis solution flow rate (Qd)>600 ml/min to 800 ml/min>Assess access &/or needle placement for problems
69Nocturnal/Home Dialysis >3x/week, decreased blood flows, longer treatmenttimesHome Dialysis>5-6 times per week, shorter treatment timesSince both treatment modalities lead to feeling better/improved lab results; challenges current concepts of “adequacy”
70PET (Peritoneal Equilibrium Test) Transport of substances is a function of peritoneal membrane area times permeability, so a test is useful todetermine the function of the peritoneal membrane>Assesses rate at which solutes (substance dissolved influid) equilibrate between the peritoneal capillaryblood and dialysate>Solutes = creatinine, urea, phosphate, proteinscommonly measured>Dextrose concentration responsible for UF
72Diffusion - the process by which molecules spread from areas of high concentratiion, to areas of low concentration. When the molecules are even throughout a space - it is called EQUILIBRIUMWatch this animation of water molecules moving across a selectively permeable membrane. Water molecules are the small blue shapes, and the solute is the green.The solute is more concentrated on the right side to start with, which causes molecules to move across the membrane toward the left until equilibrium is reached.
73PET Standardized 4-hour procedure >Measures dialysate creatinine and glucose levels at 0,2 and 4 hours after dialysis solution is infused into theabdomen and serum creatinine and glucose levels atany time during the test.>Performed several weeks after PD initiated and whenclinical problems arise, e.g. suspect alteredmembrane transport
74PETTransport rates assessed by calculating the rates when equilibrium is reached between the peritoneal blood and dialysate>D/P ratio = solute concentration in dialysate/solute concentration in plasma (blood)>D/DO = Decrease in dialysate glucose concentrationover timeExpressed as standard deviation (SD)—SD tells you how much variation from the average
77Rapid Transporters Those with high rates of diffusion/osmosis >Transport small molecules (e.g. urea, creatinine,glucose) quickly>Leads to equilibration between dialysate and bloodearly in the dwell>If fluid left in peritoneum, it will be continuouslyabsorbed by the lymphatics, potentially leading topoor UF and volume expansion>Do best with short dwell times>May benefit from icodextrin dialysate solution>Poorly absorbed so osmotic gradient maintained
78Decreased Clearance? Increasing BUN and creatinine could be due to: >Poor compliance>High protein intake or metabolic acidosis>Decreased peritoneal permeability>Slow transporter>UF continues through out the dwell; clearancecontinues through out long dwell exchange>Increase inflow dialysate volumes to increaseclearance
79Interpreting PET Results If clearance unchanged but UF decreased>Could be due to increased lymph absorptionor catheter malfunctionIf PET shows increased clearance>? Peritonitis>If UF inadequate ? membrane failureIf PET shows decreased clearance and decreased UF>? membrane failure
80PETTest can be used to:>Predict dialysis dose (# cycles and dwell duration)>Help choose peritoneal dialysis regimen>Classify peritoneal dialysis transport (rapid and slowtransporters)>Calculate creatinine clearance>CCL = (D/P) X VPeritoneal characteristics change over time>Peritonitis—problems with UF common due toincrease glucose absorption that occurs during infection
81Take Home Points For Adequacy While we can measure urea, it is one of the less toxic waste products. Currently there is no way to measure all the toxins that accumulate in the blood.While Kt/V and URR help us to measure outcomes, they have limitations.In the end, it is as important to look at the entire clinical picture as it is to calculate Kt/V and URR.>How does the person feel?>Is his/her weight stable?PET results can help>Determine dwell times and # cycles needed to clear toxins.>Confirm impending membrane failure.
83ReferencesCoyne, D.W., Kapoian, T., Suki, W., Singh, A.K., Moran, J.E., Dahl, N.V., and Rizkala, A.R (2007). Ferric gluconate is highly efficacious in anemic hemodialysis patients with high serum and low transferrin saturation: results of the Dialysis Patients’ Response to IV Iron with Elevated Ferritin (DRIVE) Study. Journal of American Society of Nephrology,(3),retrieved August 16, 2011.KDOQI Clinical Practice Guidelines and Clinical Practice Recommendations for Anemia in Chronic Kidney Disease. Retrieved August 25, 2011 from
84ReferencesKDOQI Clinical Practice Guidelines and Clinical Practice Recommendations for Anemia in Chronic Kidney Disease: 2007 Update of Hemoglobin Target. Retrieved August 25, 2011 fromKDOQI Clinical Practice Guidelines and Clinical Practice Recommendations 2006 Updates for Hemodialysis Adequacy and Peritoneal Adequacy. Retrieved August 16, 2011 from HD_PD/pd_guide2.htm
85ReferrencesLy, J., Marticorean, R., Donnelly S., (2004). Red blood cell survival in chronic renal failure. American Journal of Kidney Diseases, 44(4),National Kidney Foundation (2001). KDOQI clinical practice guidelines for hemodialysis adequacy. American Journal of Kidney Diseases, 37, supp 1, S7-64.
86ReferencesYavuz, A., Tetta, C., Ersoy, F., D’initin, V., Ratanaret, R., De Cal, M., Borello, M., Bordoni, V., Savatori, G., Andrikes, E., Yakapoglu, E., Levin, N., & Ronco, C., (2005) Uremic toxins: A new focus on an old subject. Seminars in Dialysis, 18 (3),