1、.2 Medicine Housestaff Conference 2/13/2009 Margaret A Kiser MD PhD, .3+Chronic Kidney Disease Definitions Epidemiology+Screening for CKD+Treating Complications of Advanced CKD Hypertension Control of volume Alterations in bone metabolism Anemia Nutrition Hyperkalemia+Suggested K-DOQI action plan ba
2、sed on disease severity+When to refer and why+Slowing Progression of CKD+Evidence supporting antihypertensive use+Cardiovascular Risk Modification+Getting the word out.4What is Chronic Kidney Disease?.5+Kidney damage for 3 months as defined by structural or functional abnormalities of the kidney, wi
3、th or without decreased GFR, manifest by either: Pathological abnormalities; or Markers of kidney damage, including abnormalities in the composition of the blood or urine, or abnormalities in imaging testing+Glomerular Filtration Rate (GFR) 60 ml/min/1.73 m2 for 3 months, with or without structural
4、kidney damage.619,000,000Chronic KidneyDisease372,000Dialysis80,000Transplant.7Proposed NKF-K/DOQI Guidelines. NKF Clinical Nephrology Meetings 2001; Orlando, Fla.5040302015GFR (mL/min/1.73 m2) 1Kidney Damage 2Mild GFR 3Moderate GFR 4Severe GFR 60708090 5KidneyFailureCKD Continuum“CKD”ESRD 6 RRT.8 G
5、FRPrevalence in US Pop.* StageDescription(mL/min/1.73 m2) N (1,000s)%*Population of 177 million adults age over 20* with presence of proteinuria or hematuria +/- structural changes* do not need proteinuria or hematuria, just GFR 60yrs Family history of kidney disease Exposure to drugs or procedures
6、associated with an acute decline in kidney function Kidney donors and transplant recipients (AJKD, 39, 2002, pS214).13.14+GFR can be assessed by the renal clearance of a substanceClearance of substance X (Cx) = UxVx/SxRecall GFR * Sx = UxVx (amount filtered = amount excreted) Cx = UxV/Sx Cx = GFR+Tw
7、o important assumptions: Marker neither secreted or absorbed Steady state+Examples of markers: inulin, iothalamate, iohexol, serum creatinine, cystatin-C.15+Methods of calculation Cockcroft-Gault formula MDRD formula/modified MDRD.16The Cockcroft-Gault calculation GFR ml/min/1.73m2 = (140-age) x Lea
8、n 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+0.318+Modified MDRD Formula186.338 x SCr-1.154 x Age-0.203 x 1.212 if black x 0.742 if femaleMDRD GFR*From Levey et al, 1999Ann Intern Med 130: 461-470(A calc
9、ulator 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 26.9142.7 66.152.3(Calculated with Cockcroft-Gault).19+Based on the assumption that in the presence of stable GFR, urine creatinine and protein excretion constant+Ginsberg et al first
10、 demonstrated a strong correlation between single Urine P/C and 24 h urine in 46 ambulatory patients at a single center, r=0.97+Important caveats Lean body mass Timing of urine collectionRelationship of spot and 24 urine proteinGroup A: Low creatinine excretion, slope=1.11Group B: Intermediate Cr ex
11、cretion, slope=0.97Group C: High Cr excretion, slope = 0.77.20Fig 1 Correlation between ln spot morning urine protein:creatinine ratio and log 24 hour urinary protein in 177 non-diabetic patients with chronic nephropathies and persistent clinical proteinuria.21+Increased single nephron GFR+Afferent
12、arteriolar vasodilation+Intraglomerular hypertension+Loss of glomerular permselectivity+Inabilty to appropriately dilute or concentrate the urine in the face of volume challenge.22+Glomerular hypertrophy+Focal segmental glomerulosclerosis with hyalinosis+Interstitial fibrosis+Vascular sclerosis+Epit
13、helial foot process fusion .23Nephron MassGlomerular Volume andGlomerular HypertensionEpithelial Cell Density andFoot Process FusionGlomerular Sclerosisand HyalinosisPrimary InsultProteinuria.24.25+Recommendations for Anti-hypertensives in Patients with Chronic Kidney Disease Treatment is indicated
14、at any stage of the disease Use 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).26AfferentArterioleEfferent ArterioleDihydropyridinesNifedipineFelodipineAmlodipineVasodilate PressureARBVerap
15、amilDiltiazemVasodilatePressureVasoconstrictACE-I.27Bakris. J Clin Hypertens 1999;1:141.28ACE-IARB -BlockersThiazide DiureticsVasodilators - BlockersCentral AgentsCCBs.29% Filtered Na+Site of Action Diuretic ExcretedNa+-K+-2Cl- carrier Furosemide in Loop of Henle Bumetanide 20 %TorsemideEthacrynic a
16、cidNa+-Cl- carrier Thiazides 3-5 % in the distal tubule MetolazoneNa+ channel in the Amiloride 1-2 % cortical collectingTriamterene ductSpironolactone (indirect).30GFR 150 ml/minGFR 15 ml/min1250 mEq125 mEq250 mEq25 mEq.31+Type I: Short-term Decrease in the response to a diuretic after the first dos
17、e Teleologically- appropriate response to volume depletion+Type II: Long-term Hypertrophy of distal nephron segments allowing greater sodium resorption.32Renal Insufficiency CrCl 50Loop DiureticDetermine Effective Dose: 5-10X Usual DoseAdminister as Frequently as NecessaryThiazide According to CrCl
18、50ml/min50-100mg/ 50-100mg/ 25-50mg/ day day dayADDAdd Distal Diuretic DrugFrom Brater DG N Eng J Med 1998;339:387.33.34 PTHPiCa2+Renal Mass25(OH)D31,25(OH)2D31-alpha-hydroxylase1-alpha-hydroxylase+Acidosis+Hyperparathyroid Related Bone DiseaseImpairedAbsorptionOsteitis FibrosaCystica.35Reduced Rena
19、l Mass GFR 654070pg/ml and supplementation instituted if necessary, a level of 30ng/ml is abnormal and 15ng/ml, moderate to severe+Treatment 2.7- 4.6 mg/dL Ca X Phos 2.7-/= 4.6mg/dL Ca X Phos 30pg/ml and PTH-I target, initiate treatment with exogenous “Active Vitamin D” A few patients with very elev
20、ated PTH-I values may benefit from Calcimimetics (AJKD, 39, 2002, pS214).39+High Phosphorus FoodsDairy products (Cheese, ice cream, milk), nuts, peanut butter, biscuits, processed meats-hotdogs, chocolate, dark sodas (Coke, Pepsi), beans +Lower Phosphorus ChoicesCream cheese, sour cream, Ginger ale/
21、sprite, sherbet, non-dairy creamer.40+Given with meals, timing essential +Aluminum based medicines; (Basaljel, Amphogel)+Calcium Based Calcium Carbonate/Magnesium Carbonate (Magnebind) Calcium Carbonate (Tums, Calcichew, Calcimix) Calcium Acetate (Phoslo).41+The use of calcium based binders is now f
22、alling out of favor because of the recognition of accelerated vascular calcification proposed to be associated with them (Disputed by the manufacturers of same) Sevelamer hydrochloride (“Renagel”), cationic polymer, binds phosphate thru ion exchange, can promote/worsen metabolic acidosis New product
23、 Sevelamer carbonate (“Renvela”) does not lead to acidosis Lanthanum carbonate (“Fosrenol”), long term effects unknown VERY EXPENSIVE (Sevelamer 800mg 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+Several Vitam
24、in D sterols are now available to replace naturally occurring 1,25 Vitamin - D3 , levels of which fall with declining renal mass Rocaltrol (Calcitriol, oral) Doxercalciferol (Hectoral , D2 prohormone, available in oral and parenteral forms) Paracalcitol (Zemplar), oral and parenteral forms available
25、 .43+In compliant patients with stable renal function, Initiate “Active Vitamin 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
26、x 3months then q 3 months and check PTH-I q 3 months+Monitor closely because of the significant risk of developing hypercalcemia (AJKD, 39, 2002, pS214).44CalciumSensing Receptor(CaR)Cinacalcet (Sensitizes CaR to Ca2+)NucleusVDRVitamin D Serum CalciumPTHInhibitoryStimulatoryCellularProliferationThe
27、parathyroid cell.45Calcimimetic agents+Rapid onset (hours)+Inhibit PTH secretion+Inhibit PTH synthesis+Inhibit parathyroid cellular proliferation+Decrease serum calciumVitamin D Sterols+Act on genomic receptor+Slow onset (days to weeks)+Inhibit PTH synthesis+Increase serum calcium.46PhosphorusCa2+1,
28、25(OH)2D3(Use Cautiously)New Paradigm in Treatment of Secondary HyperparathyroidismNon-calciumBased BindersCinacalcetPTH.47+Tertiary hyperparathyroidism+Renal osteodystrophy Demineralization Bone pain Fractures+Systemic toxicity Cutaneous - Calciphylaxis Cardiovascular, accelerated vascular calcific
29、ation Nervous.48.49.50+Indication Bio-Intact PTH 800 pg/mL refractory to medical therapy Severe hypercalcemia Progressive high turnover bone disease+Complications May result in excessive low PTH levels Symptomatic hypocalcemia Risk for injury to recurrent laryngeal nerve.51+Develops when the GFR dec
30、reases to 200, TSAT 20% Oral agentsChromagen: 33% ironFerrous sulfate: 20% ironNiferex (Polysaccharide with Vit C): 150mg elemental ironFerrous fumurate: 33% ironFerrous gluconate (Fergon): 12% iron Oral agents do not work well, primarily b/o ill tolerated GI side effects.54 n Balancing the impact o
31、f decreased protein intake on the rate of progression of renal disease, against hypoalbuminemia and malnutritionn Can we restrict protein intake sufficiently, without leading to malnutrition, especially important in patients with eGFR 25 ml/min.55Obrador et al. J Am Soc Nephrol 1999; 10; p. 1795Mean
32、 3.2 +/- 0.7Median 3.3.56Lowrie, Seminars in Dialysis. Vol 10, No 2 (Mar-Apr) 1997, p. 1161994 Data4.50.50.71.01.52.02.53.04.05.06.08.010.012.014.0Albumin (gm/dl)Odds Ratio of DeathAlbuminunadj.Case Mixadj.Case Mix+ Lab adj.Referenceare not different fromBars without symbols = p .05 = p 90Stage 2: G
33、FR 60-89Stage 3: GFR 30-59Stage 4: GFR 15-29Stage 5: GFR 15Clinical evaluationSlowing ProgressionCVD Risk ReductionReplacementTherapySymptom control &preparation for replacement therapySlowing ProgressionCVD Risk ReductionTreat Complication.66+ACE Inhibitor, Angiotensin II Receptor Antagonist, and B
34、eta Blocker Therapy, to control HTN+Adequate volume control with diuretics+Early Treatment of hyperphosphatemia with Phosphate binders +Early Treatment with Active Vitamin D +Early Treatment with Erythropoietin/Darbepoetin (PROCRIT/ARANESP)+Early Treatment with Iron Products+Aggressive control of glucose levels in Diabetics.67THE END
