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Chronic Kidney Disease

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  • 1. MANAGEMENT OF THE PATIENT WITH CHRONIC KIDNEY DISEASE Medicine Housestaff Conference2/13/2009Margaret A Kiser MD PhD,

2. Outline 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 based on disease severity When to refer and why Slowing Progression of CKD Evidence supporting antihypertensive use Cardiovascular Risk Modification Getting the word out 3. What is Chronic Kidney Disease? 4. Defining CKD Kidney damage for 3 months as defined by structural or functional abnormalities of the kidney, with 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 kidney damage 5. Estimates of U.S. Chronic Kidney DiseasePopulation in 200019,000,000 ChronicKidney Disease 372,000 80,000DialysisTransplant 6. Stages of CKDCKD Continuum CKDESRD 1 2 3 45 6 KidneyMild ModerateSevereKidneyRRT Damage GFRGFRGFR Failure 90 80 70 6050 4030 20 90**10,2595.8 2 Mild GFR 60 89**5,300 7,100 34 3 Moderate GFR 30 59***7,5533.3 4 Severe GFR 15 29363 0.2 5 Kidney failure < 15 or dialysis 300 0.112.4 13.4*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 associated with an acute decline in kidney function Kidney donors and transplant recipients (AJKD, 39, 2002, pS214) 12. Relationship of Serum Creatinine to GFR 13. Estimation of GFR GFR can be assessed by the renal clearance of a substance Clearance of substance X (Cx) = UxVx/Sx Recall GFR * Sx = UxVx(amount filtered = amount excreted)Cx = UxV/SxCx = GFR Two important assumptions: Marker neither secreted or absorbed Steady state Examples of markers: inulin, iothalamate, iohexol, serum creatinine, cystatin-C 14. Calculation of GFR Methods of calculation Cockcroft-Gault formula MDRD formula/modified MDRD 15. The Cockcroft-Gault calculationGFR ml/min/1.73m2 = (140-age) x Lean BW Kg72 x S creatinine mg%( x 0.85 for Females ) 16. MDRD GFR 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 MDRDFormula 186.338 x [SCr]-1.154 x [Age]-0.203 x [1.212 if black] x [0.742 if female](A calculator may be found at www.hdcn.org)*From Levey et al, 1999Ann Intern Med 130: 461-470 17. 84 F 22 M66 M66 F Wt (kg) 45.5 104.5 77.2 71.8 Screat1.21.2 1.2 1.2 eGFR 26.9142.766.152.3(Calculated with Cockcroft-Gault) 18. Urine Protein / Creatinine Ratio Based on the assumption that in the presence of stable GFR, urine creatinine and protein excretion constant Ginsberg 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=0.97 Important caveats Lean body mass Timing of urine collection Relationship of spot and 24 urine protein Group A: Low creatinine excretion, slope=1.11 Group B: Intermediate Cr excretion, slope=0.97 Group C: High Cr excretion, slope = 0.77 19. Fig 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 20. Physiologic Changes in ChronicKidney Disease Increased single nephron GFR Afferent arteriolar vasodilation Intraglomerular hypertension Loss of glomerular permselectivity Inabilty to appropriately dilute or concentrate the urine in the face of volume challenge 21. Anatomic and Histologic Features Due to Glomerular Hypertension Glomerular hypertrophy Focal segmental glomerulosclerosis with hyalinosis Interstitial fibrosis Vascular sclerosis Epithelial foot process fusion 22. Pathogenesis of SecondaryGlomerulosclerosisPrimary Insult Nephron Mass Glomerular Sclerosis Glomerular Volume and and Hyalinosis Glomerular Hypertension Epithelial Cell Density and Foot Process Fusion Proteinuria 23. Hypertension in CKD 24. Recommendations for Anti-hypertensives in Patients with Chronic Kidney Disease Treatment is indicated 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) 25. Effects of Various Anti-hypertensives onGlomerular Capillary PressureAfferent EfferentArteriole Arteriole ACE-IPressure Vasoconstrict Vasodilate Vasodilate PressureARB DihydropyridinesVerapamil NifedipineDiltiazem Felodipine Amlodipine 26. Number of Medications to Achieve Goal BP in 5 Trials of DM/Renal DiseaseUKPDS ( 4.6 Calcitriol 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 months Monitor closely because of the significant risk of developing hypercalcemia (AJKD, 39, 2002, pS214) 43. The Calcimemetics Serum Calcium Calcium Sensing Receptor Cinacalcet (Sensitizes CaR to Ca2+) (CaR)Stimulatory Cellular Proliferation NucleusPTH VDRInhibitory Vitamin DThe parathyroid cell 44. Treatment of SecondaryHyperparathyroidismCalcimimetic agentsVitamin D Sterols Rapid onset (hours) Act on genomic receptor Inhibit PTH secretion Slow onset (days to Inhibit PTH synthesisweeks) Inhibit parathyroid Inhibit PTH synthesis cellular proliferation Increase serum calcium Decrease serum calcium 45. New Paradigm in Treatmentof Secondary Hyperparathyroidism PhosphorusCinacalcetNon-calcium Based BindersPTHCa2+1,25(OH)2D3(Use Cautiously) 46. Complications of Long Term Calcium and Phosphorus imbalance Tertiary hyperparathyroidism Renal osteodystrophy Demineralization Bone pain Fractures Systemic toxicity Cutaneous - Calciphylaxis Cardiovascular, accelerated vascular calcification Nervous 47. Parathyroidectomy 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 48. Anemia of Chronic Kidney Disease Develops when the GFR decreases to < 30-35 ml/min decreasing production of erythropoietin 2/2 reduced renal mass Uremic inhibition of bone marrow Decreased RBC life-span PTH induced marrow fibrosis Iron deficiency Aluminum related bone disease Normochromic, normocytic 49. Why Treat Anemia?175-Patient CKD Study 6%increasein risk of1g/dLdecrease in Hgb=LVH P = 0.0062 Levin et al. Am J Kidney Dis. 1996;27:347-354. 50. Anemia-Treatment Guidelines Goal Hgb 11-12 Recombinant erythropoeitin Epogen/Procrit 50-150 U/kg/wk SQ Darbopoetin 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 range Recent concerns re increased risk of cardiovascular events associated with an elevated Hgb in association with use of high doses of these products Iron Goal Ferritin >200, TSAT >20% Oral agents Chromagen: 33% iron Ferrous sulfate: 20% iron Niferex (Polysaccharide with Vit C): 150mg elemental iron Ferrous fumurate: 33% iron Ferrous gluconate (Fergon): 12% iron Oral agents do not work well, primarily b/o ill tolerated GI side effects 51. Nutrition Balancing 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 52. Serum Albumin at the Start of Dialysis in the U.S. ESRD Population35% Mean 3.2 +/- 0.7 Median 3.330% 30% 25%22% 23%20%15% 15%10% 10% 5% 0%4.5 1994 Data Albumin (gm/dl) Lowrie, Seminars in Dialysis. Vol 10, No 2 (Mar-Apr) 1997, p. 116 54. Hyperkalemia A common reason for initiation of RRT The kidney is the only route for excretion of dietary intake, thus there is limited excretion as GFR falls, potentially leading to increased serum levels Many patients with CKD also have a tendency to retain potassium because of stimulation of the Renin/Angio/Aldo system Diabetics may have a type IV RTA (hyporeninemic hyperaldosteronism) Use of ACE-I can exacerbate hyperkalemia 55. Hyperkalemia Treatment Restriction of intake Diuretics Kayexelate, long term use can lead to colonic mucosal defects 56. Hyperkalemia High Potassium foodsFruitsVegetablesOther foods ApricotArtichokeBran/bran products AvocadoAsparagusCoffee, Tea Banana BeansChocolate Cantaloupe, Honeydew Brussel sproutsCoconut, Granola Dates,Figs, dried fruits Lentils, legumes Molasses Mango,Papaya Limas, Peas, OkraMilk, Ice cream Orange, NectarineParsnips, Rutabaga Nuts/seeds Peaches, PrunesPotatoes Snuff/chewing tobacco Raisins, PersimmonsTomatoes Salt subs/Lite salt Juices of theseWinter squashfruitsSalt free veg. juice 57. Hyperkalemia Low Potassium foods Fruits VegetablesStarches Apples/applesauce BroccoliRice BlackberriesBeans, green/waxNoodles Blueberries/Cranberries Beets/carrots/corn Bread/bread products Cherries/grapes/gooseberries Cabbage/cauliflowerCereals Fruit cocktail Cucumber, lettuceCakes, cookies Pears, canned/pineappleEggplant/onionsPies (not chocolate or Plums/raspberries/Strawberries Summer squashhigh K fruit) Mandarin oranges/Tangerines Mushrooms, raw Rhubarb, WatermelonParsley, radish, turnip Juices of these fruits Greens (collards, kaleturnip, mustard) Peas, green 58. Cardiovascular Risk Individuals with CKD are at increased risk for CVD, they should be considered in the highest risk group for evaluation and management according to NKF recommendations. Remember, there are an estimated 7.5 million people in the US with stage 3 CKD and 363,000 at Stage 4 CKD but only 372,00 on dialysis with only a further 80,000 having received a kidney transplant. If we consider the patients at Stages 3 and 4, they have a higher risk of death than progressing to need for dialysis !!!! 59. When to Refer to Nephrology:General Indications Serum Creatinine >/= 1.7 mg/dl (M) and >/= 1.4 (F) Poorly controlled HTN Diabetes mellitus with atypical renal manifestations Proteinuria or nephrotic syndrome without retinopathy Renal insufficiency without proteinuria or retinopathy Sudden onset of nephrotic syndrome or rapidly changing serum creatinine Systemic disease associated with renal involvement Heavy proteinuria Urine-sediment abnormalities Prior to onset of uremic symptoms 60. Goals of Early Referral Patient education, soon Medicare reimbursement for CKD education Choice of modality: HD vs PD vs Transplant Planning of vascular access if HD is the chosenintervention and catheter placement if PD Planning of timing of transplantation work-up Institution of interventions to slow progression of renal disease 61. Avoidance of acute exacerbation of function Volume depletion IV Radiographic contrast Gadolinium Aminoglycosides and amphoterecin NSAIDS/COX II inhibitors (Tordal) ACE-I/ARB in certain populations CyA / Tacrolimus in the transplant population Obstructive uropathy 62. K-DOQI Action Plan for theManagement of CKD Stage 1: GFR > 90Clinical evaluationSlowing ProgressionCVD Risk ReductionStage 2: GFR 60-89 Slowing ProgressionStage 3: GFR 30-59 CVD Risk Reduction Treat Complication Symptom control & Stage 4: GFR 15-29 preparation forreplacement therapyStage 5: GFR < 15Replacement Therapy 63. In Summary: Important Early Conservative Therapies ACE Inhibitor, Angiotensin II Receptor Antagonist, and Beta 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 64. THE END