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1、,.,2,MANAGEMENT OF THE PATIENT WITH CHRONIC KIDNEY DISEASE,Medicine Housestaff Conference 2/13/2009 Margaret A Kiser MD PhD,.,3,Outline,Chronic Kidney DiseaseDefinitions EpidemiologyScreening for CKDTreating Complications of Advanced CKDHypertensionControl of volumeAlterations in bone metabolismAnem
2、iaNutritionHyperkalemiaSuggested K-DOQI action plan based on disease severityWhen to refer and whySlowing Progression of CKDEvidence supporting antihypertensive useCardiovascular Risk ModificationGetting the word out,.,4,What is Chronic Kidney Disease?,.,5,Defining CKD,Kidney damage for 3 months as
3、defined by structural or functional abnormalities of the kidney, with or without decreased GFR, manifest by either:Pathological abnormalities; orMarkers of kidney damage, including abnormalities in the composition of the blood or urine, or abnormalities in imaging testingGlomerular Filtration Rate (
4、GFR) 60 ml/min/1.73 m2 for 3 months, with or without structural kidney damage,.,6,Estimates of U.S. Chronic Kidney Disease Population in 2000,19,000,000,Chronic KidneyDisease,372,000,Dialysis,80,000,Transplant,.,7,Stages of CKD,Proposed NKF-K/DOQI Guidelines. NKF Clinical Nephrology Meetings 2001; O
5、rlando, Fla.,6 RRT,.,8,Prevalence of CKD,1Kidney damage 90*10,259 5.82Mild GFR 60 89*5,300 7,100 3 43Moderate GFR 30 59*7,553 3.34Severe GFR 15 29363 0.25Kidney failure 15 or dialysis300 0.112.4 13.4,GFRPrevalence in US Pop.* StageDescription(mL/min/1.73 m2) N (1,000s)%,*Population of 177 million ad
6、ults age over 20* with presence of proteinuria or hematuria +/- structural changes* do not need proteinuria or hematuria, just GFR 60,.,9,AGE AND RACE,Further, African Americans develop ESRD at a younger age 55.8 vs 62.2 yoAlthough only 12.6% of the US population, African Americans constitute 50% of
7、 the ESRD population,Point prevalence of ESRD,USRDS 2007 Annual Report AJKD 51, Suppl 1, Jan 2008,.,10,Familial Influences,Inherited NephropathiesFamily history is a strong risk factor for diabetic nephropathyIn all ethnic groups studied to date diabetic siblings of pts with ESRD 2/2 DM were at mark
8、edly increased risk of developing ESRD.Particularly common in African Americans with an increased incidence rate of 4-25 fold greater than Caucasians,AJKD 2008, 51 (1), 29-37,.,11,Etiology of Chronic Kidney Disease,USRDS 2001,.,12,Identifying patients at risk:National Kidney Foundation Recommendatio
9、ns (KDOQI),Individuals at increased risk for CKD should be tested at the time of health evaluations to determine if they have CKD. This should include patients with:-DM HTN Autoimmune diseases Chronic systemic infectionsRecovery from acute renal failureAge 60yrsFamily history of kidney disease Expos
10、ure to drugs or procedures associated with an acute decline in kidney functionKidney donors and transplant recipients,(AJKD, 39, 2002, pS214),.,13,Relationship of Serum Creatinine to GFR,.,14,Estimation of GFR,GFR can be assessed by the renal clearance of a substanceClearance of substance X (Cx) = U
11、xVx/SxRecall GFR * Sx = UxVx (amount filtered = amount excreted) Cx = UxV/Sx Cx = GFRTwo important assumptions:Marker neither secreted or absorbedSteady stateExamples of markers: inulin, iothalamate, iohexol, serum creatinine, cystatin-C,.,15,Calculation of GFR,Methods of calculationCockcroft-Gault
12、formulaMDRD formula/modified MDRD,.,16,The Cockcroft-Gault calculation,GFR ml/min/1.73m2 = (140-age) x Lean BW Kg 72 x S creatinine mg% ( x 0.85 for Females ),.,17,MDRD GFR Formula*170 x SCr-0.999 x Age-0.176 x 0.762 if female x 1.180 if black x Alb+0.318Modified MDRD Formula186.338 x SCr-1.154 x Ag
13、e-0.203 x 1.212 if black x 0.742 if female,MDRD GFR,*From Levey et al, 1999Ann Intern Med 130: 461-470,(A calculator may be found at www.hdcn.org),.,18,84 F 22 M 66 M 66 F Wt (kg) 45.5 104.5 77.2 71.8 Screat 1.2 1.2 1.2 1.2,eGFR,26.9,142.7,66.1,52.3,(Calculated with Cockcroft-Gault),.,19,Urine Prote
14、in / Creatinine Ratio,Based on the assumption that in the presence of stable GFR, urine creatinine and protein excretion constantGinsberg et al first demonstrated a strong correlation between single Urine P/C and 24 h urine in 46 ambulatory patients at a single center, r=0.97Important caveatsLean bo
15、dy massTiming of urine collection,Relationship of spot and 24 urine protein,Group A: Low creatinine excretion, slope=1.11Group B: Intermediate Cr excretion, slope=0.97Group C: High Cr excretion, slope = 0.77,.,20,Fig 1 Correlation between ln spot morning urine protein:creatinine ratio and log 24 hou
16、r urinary protein in 177 non-diabetic patients with chronic nephropathies and persistent clinical proteinuria,.,21,Physiologic Changes in ChronicKidney Disease,Increased single nephron GFRAfferent arteriolar vasodilationIntraglomerular hypertensionLoss of glomerular permselectivityInabilty to approp
17、riately dilute or concentrate the urine in the face of volume challenge,.,22,Anatomic and Histologic Features Due to Glomerular Hypertension,Glomerular hypertrophyFocal segmental glomerulosclerosis with hyalinosisInterstitial fibrosisVascular sclerosisEpithelial foot process fusion,.,23,Pathogenesis
18、 of Secondary Glomerulosclerosis,Nephron Mass,Glomerular Volume andGlomerular Hypertension,Epithelial Cell Density andFoot Process Fusion,Glomerular Sclerosisand Hyalinosis,Primary Insult,Proteinuria,.,24,Hypertension in CKD,.,25,Recommendations for Anti-hypertensives in Patients with Chronic Kidney
19、 DiseaseTreatment is indicated at any stage of the diseaseUse drugs that lower glomerular capillary pressure (ACE inhibitors, ARB, verapamil and diltiazem) Goal is to keep the blood pressure 130/80 mmHg ( 120 SBP in DM),.,26,Effects of Various Anti-hypertensives on Glomerular Capillary Pressure,Affe
20、rentArteriole,Efferent Arteriole,DihydropyridinesNifedipineFelodipineAmlodipine,Vasodilate,Pressure,ARBVerapamilDiltiazem,Vasodilate,Pressure,Vasoconstrict,ACE-I,.,27,Number of Medications to Achieve Goal BP in 5 Trials of DM/Renal Disease,Bakris. J Clin Hypertens 1999;1:141.,.,28,A Hierarchy of Age
21、nts,ACE-IARB,-BlockersThiazide Diuretics,Vasodilators- BlockersCentral Agents,CCBs,More Preferred,Less Preferred,.,29,Volume Management-Diuretics,% Filtered Na+Site of Action Diuretic ExcretedNa+-K+-2Cl- carrierFurosemide in Loop of Henle Bumetanide 20 %TorsemideEthacrynic acidNa+-Cl- carrier Thiazi
22、des 3-5 % in the distal tubule MetolazoneNa+ channel in theAmiloride 1-2 % cortical collectingTriamterene ductSpironolactone (indirect),.,30,Natriuretic Response to Furosemide at Different Levels of Renal Function,GFR 150 ml/min,GFR 15 ml/min,1250 mEq,125 mEq,250 mEq,25 mEq,.,31,Diuretic Tolerance,T
23、ype I: Short-termDecrease in the response to a diuretic after the first doseTeleologically- appropriate response to volume depletionType II: Long-termHypertrophy of distal nephron segments allowing greater sodium resorption,.,32,Algorithm for Diuretic Use,Renal Insufficiency CrCl 50,Loop DiureticDet
24、ermine Effective Dose: 5-10X Usual DoseAdminister as Frequently as Necessary,Thiazide According to CrCl 50ml/min50-100mg/ 50-100mg/ 25-50mg/ day day day,ADD,Add Distal Diuretic Drug,From Brater DG N Eng J Med 1998;339:387,.,33,Alterations in Bone and Mineral Metabolism,.,34,PTH,Pi,Ca2+,Renal Mass,25
25、(OH)D3,1,25(OH)2D3,1-alpha-hydroxylase,1-alpha-hydroxylase,+,Acidosis,+,Hyperparathyroid Related Bone Disease,ImpairedAbsorption,Osteitis FibrosaCystica,.,35,Reduced Renal Mass,GFR, 65,40,25,Increased PTH Secretion,Decreased 1,25-D,Hyperphosphatemia,Hypocalcemia,.,36,Calcium and Phosphorus Balance:N
26、ational Kidney Foundation Recommendations (KDOQI),In addition, it has become clear that CKD patients have a nutritional deficiency of 25-OH Vitamin D which itself leads to an increase in PTH secretionLevels of 25-OH D should be measured when PTH-Intact 70pg/ml and supplementation instituted if neces
27、sary, a level of 30ng/ml is abnormal and 15ng/ml, moderate to severeTreatment5ng/ml 50,000U Ergocalciferol/wk x12, then q mo x65-15ng/ml 50,000/wk x 4, then q mo x 616-30ng/ml 50,000/month x 6Measure 25(OH)-D at 6monthsMaintenance 800-1200 IU qd,(AJKD, 39, 2002, pS214),.,37,Calcium and Phosphorus Ba
28、lanceKDOQI Recommendations,Stage 3 CKD, GFR 30-59Measure Ca, Phos and PTH-I every 12 monthsTarget levelsCalcium WNL for labPhos 2.7- 4.6 mg/dLCa X Phos 55PTH-I 30-70 pg/ml,Stage 4 CKD, GFR 15-29Measure Ca, Phos and PTH-I every 3 monthsTarget levelsCa preferably WNL for labPhos 2.7-/= 4.6mg/dLCa X Ph
29、os 55PTH-I 70-110 pg/ml,.,38,Calcium and Phosphorus BalanceKDOQI Recommendations,How are these goals achieved ?Control of dietary phosphorus intake to 0.8-1g/dMay need initiation of “Phosphate binders” with mealsWhen 25(OH)-D 30pg/ml and PTH-I target, initiate treatment with exogenous “Active Vitami
30、n D”A few patients with very elevated PTH-I values may benefit from Calcimimetics,(AJKD, 39, 2002, pS214),.,39,Calcium and Phosphorus Balance:Limit Phosphorus intake to 0.8-1.0 g/d,High Phosphorus FoodsDairy products (Cheese, ice cream, milk), nuts, peanut butter, biscuits, processed meats-hotdogs,
31、chocolate, dark sodas (Coke, Pepsi), beans Lower Phosphorus ChoicesCream cheese, sour cream, Ginger ale/sprite, sherbet, non-dairy creamer,.,40,Use of Phosphate binders,Given with meals, timing essential Aluminum based medicines; (Basaljel, Amphogel)Calcium BasedCalcium Carbonate/Magnesium Carbonate
32、 (Magnebind)Calcium Carbonate (Tums, Calcichew, Calcimix) Calcium Acetate (Phoslo),.,41,Use of Phosphate binders,The use of calcium based binders is now falling out of favor because of the recognition of accelerated vascular calcification proposed to be associated with them (Disputed by the manufact
33、urers of same)Sevelamer hydrochloride (“Renagel”), cationic polymer, binds phosphate thru ion exchange, can promote/worsen metabolic acidosisNew product Sevelamer carbonate (“Renvela”) does not lead to acidosisLanthanum carbonate (“Fosrenol”), long term effects unknownVERY EXPENSIVE (Sevelamer 800mg
34、 tab $1.93 each, dose varies 3-9 tabs a day, $173-521 each month, Fosrenol 1000mg tab $4.87 each, dose 3 tabs daily, $438 each month),.,42,Vitamin D Sterols,Several Vitamin D sterols are now available to replace naturally occurring 1,25 Vitamin - D3 , levels of which fall with declining renal massRo
35、caltrol (Calcitriol, oral) Doxercalciferol (Hectoral , D2 prohormone, available in oral and parenteral forms) Paracalcitol (Zemplar), oral and parenteral forms available,.,43,KDOQI Recommendations for use of Vitamin D sterols,In compliant patients with stable renal function, Initiate “Active Vitamin
36、 D” (1,25-OH D3) supplements when: 25-(OH)D 30pg/ml, PTH-I target, Ca 4.6Calcitriol 0.25-1.0 mcg po qd (Rocaltrol)Doxercalciferol 2.5-10 mcg po tiw (Hectoral)Paracalcitol 1-4 mcg po qd (Zemplar)Check Ca and Phos q month x 3months then q 3 months and check PTH-I q 3 monthsMonitor closely because of t
37、he significant risk of developing hypercalcemia,(AJKD, 39, 2002, pS214),.,44,The Calcimemetics,CalciumSensing Receptor(CaR),Cinacalcet (Sensitizes CaR to Ca2+),Nucleus,VDR,Vitamin D, Serum Calcium,PTH,Inhibitory,Stimulatory,CellularProliferation,The parathyroid cell,.,45,Treatment of Secondary Hyper
38、parathyroidism,Calcimimetic agentsRapid onset (hours)Inhibit PTH secretionInhibit PTH synthesisInhibit parathyroid cellular proliferationDecrease serum calcium,Vitamin D SterolsAct on genomic receptorSlow onset (days to weeks)Inhibit PTH synthesisIncrease serum calcium,.,46,Phosphorus,Ca2+,1,25(OH)2
39、D3(Use Cautiously),New Paradigm in Treatment of Secondary Hyperparathyroidism,Non-calciumBased Binders,Cinacalcet,PTH,.,47,Complications of Long Term Calcium and Phosphorus imbalance,Tertiary hyperparathyroidismRenal osteodystrophyDemineralizationBone painFracturesSystemic toxicityCutaneous - Calcip
40、hylaxisCardiovascular, accelerated vascular calcificationNervous,.,48,.,49,.,50,Parathyroidectomy,IndicationBio-Intact PTH 800 pg/mL refractory to medical therapySevere hypercalcemiaProgressive high turnover bone diseaseComplicationsMay result in excessive low PTH levelsSymptomatic hypocalcemiaRisk
41、for injury to recurrent laryngeal nerve,.,51,Anemia of Chronic Kidney Disease,Develops when the GFR decreases to 30-35 ml/min decreasing production of erythropoietin 2/2 reduced renal massUremic inhibition of bone marrowDecreased RBC life-spanPTH induced marrow fibrosisIron deficiencyAluminum relate
42、d bone diseaseNormochromic, normocytic,.,52,Why Treat Anemia?,Levin et al. Am J Kidney Dis. 1996;27:347-354.,P = 0.0062,=,1g/dL decrease in Hgb,6%increasein risk of LVH,175-Patient CKD Study,.,53,Anemia-Treatment Guidelines,Goal Hgb 11-12Recombinant erythropoeitinEpogen/Procrit 50-150 U/kg/wk SQDarb
43、opoetin alfa (ARANESP) Start 0.45mcg/kg SQ once every 2 weeks, usually dosed every three to four weeks when patient is stable in the therapeutic rangeRecent concerns re increased risk of cardiovascular events associated with an elevated Hgb in association with use of high doses of these productsIron
44、Goal Ferritin 200, TSAT 20%Oral agentsChromagen: 33% ironFerrous sulfate: 20% ironNiferex (Polysaccharide with Vit C): 150mg elemental ironFerrous fumurate: 33% ironFerrous gluconate (Fergon): 12% ironOral agents do not work well, primarily b/o ill tolerated GI side effects,.,54,Nutrition,Balancing
45、the impact of decreased protein intake on the rate of progression of renal disease, against hypoalbuminemia and malnutrition Can we restrict protein intake sufficiently, without leading to malnutrition, especially important in patients with eGFR 25 ml/min,.,55,Serum Albumin at the Start of Dialysis
46、in the U.S. ESRD Population,Obrador et al. J Am Soc Nephrol 1999; 10; p. 1795,Mean 3.2 +/- 0.7Median 3.3,.,56,Serum Albumin Concentration (gm/dl) Odds Ratio of Death,Lowrie, Seminars in Dialysis. Vol 10, No 2 (Mar-Apr) 1997, p. 116,.,57,Hyperkalemia,A common reason for initiation of RRTThe kidney is
47、 the only route for excretion of dietary intake, thus there is limited excretion as GFR falls, potentially leading to increased serum levelsMany patients with CKD also have a tendency to retain potassium because of stimulation of the Renin/Angio/Aldo systemDiabetics may have a type IV RTA (hyporenin
48、emic hyperaldosteronism)Use of ACE-I can exacerbate hyperkalemia,.,58,Hyperkalemia,TreatmentRestriction of intakeDiureticsKayexelate, long term use can lead to colonic mucosal defects,.,59,Hyperkalemia,High Potassium foods,Fruits Vegetables Other foods,Apricot Artichoke Bran/bran productsAvocado Asp
49、aragus Coffee, Tea Banana Beans ChocolateCantaloupe, Honeydew Brussel sprouts Coconut, GranolaDates,Figs, dried fruits Lentils, legumes MolassesMango,Papaya Limas, Peas, Okra Milk, Ice creamOrange, Nectarine Parsnips, Rutabaga Nuts/seedsPeaches, Prunes Potatoes Snuff/chewing tobaccoRaisins, Persimmo
50、ns Tomatoes Salt subs/Lite saltJuices of these Winter squash fruits Salt free veg. juice,.,60,Hyperkalemia,Low Potassium foods,Fruits Vegetables Starches,Apples/applesauce Broccoli RiceBlackberries Beans, green/wax NoodlesBlueberries/Cranberries Beets/carrots/corn Bread/bread productsCherries/grapes
