1. CKD 1-5d GFR Stages Complications Referral Access/ESRD  Thomas Schumacher

2. GFR  Assessment of functional renal mass  Plot course. Provides prognostic information  Provides no information as to the cause  Need imaging and UA for further information

3. Estimate of GFR  Inulin  Scans Iohexol, Iothalamate, TcDTPA,  Creatinine Clearance Cockcroft Gault MDRD CKD EPI 24 hr. urine CrCL  Cystatin C

4. Why not creatinine?  At what level of creatinine does a 65 year-old diabetic, hypertensive, white woman weighing 50 kg have CKD?

5. Why not creatinine?  At what level of creatinine does a 65 year-old diabetic, hypertensive, white woman weighing 50 kg have CKD?  77% said Creatinine >1.5 mg/dl

6. Why not creatinine?  At what level of creatinine does a 65 year-old diabetic, hypertensive, white woman weighing 50 kg have CKD?  77% said Creatinine >1.5 mg/dl  This equates to CrCl 30 mL/min, or GFR 37 mL/min/1.73m2

7. Why not creatinine?  At what level of creatinine does a 65 year-old diabetic, hypertensive, white woman weighing 50 kg have CKD?  77% said Creatinine >1.5 mg/dl  This equates to CrCl 30 mL/min, or GFR 37 mL/min/1.73m2  A Cr of 1 = GFR of 59 mL/min/1.73m2

8. Why not creatinine  A 90 Kg male has a GFR of 120 ml/min goes to a GFR of 70 ml/min.  GFR x Scr = Constant. 120 x.9 = 108 70 x X = 108, therefore X( Scr) is 1.5 but in reality his creatinine only goes to 1.2

9. Why not creatinine alone

10. Pitfalls of Creatinine as a marker of GFR  Compensatory Hyperfiltration and increased tubular secretion as GFR decreases Unrecognized Renal Disease Steady State?  Age, Race and Body Type

11. Variations in Serum Creatinine Increased Serum Creatinine decreased Serum Creatinine  Diet  Rhabdomyolysis  Medications Decrease secretion - Trimethoprim, Dronedarone, Cimetidine, Ranitidine, Famotidine, Tenofovir, Interfere with assay - Cefoxitin, Flucytosine  DKA  Supplements  Aging decreases production  Diet  Decrease muscle mass  Decreased GFR increases creatinine secretion  Nephrotic Syndrome  Sickle Cell disease

12. Classification of CKD  NKF – Kidney Disease Outcome Quality Initiative, (KDOQI ), in 2002  Modified by Kidney Disease Improvement Global Outcome,(KDIGO).

13. Definition of Chronic Kidney Disease  Kidney damage for 3 months, with or without decreased GFR 1) Pathological abnormalities 2) Biomarkers: abnormalities in composition of blood and/or urine (proteinuria/hematuria), or abnormalities in imaging tests (structural abnormalities).  GFR 3 months

14. The Purpose of staging  To guide management of risk.  Earlier identification allow therapeutic intervention sooner in the course and thus initiate treatment effective in slowing or preventing progression to ESRD as well as the sequelae of CKD 1) Hematologic – GFR <30 2) Cardiovascular – GFR <60 3) Bone – GFR < 60 4) Metabolic – GFR < 30 5) Cognitive 6) HTN

15. Chronic Kidney Disease Is Progressive

16. Stages of CKD

17. KDIEGO  Albumin to Creatinine Ratio 1) < 30 mg/g,( 1-14, 15-29 mg/g) 2) 30-299 mg/g – High Albuminuria, ( microalbuinuria ) 3) >299 mg/g - Very High Albuminuria, (Macroalbuminuria)  Stage 3a and 3b  Cause

19. Epidemic – CKD Affects 14% Of U.S. Population

20. Incidence of ESRD in US 2005  AA - 991/million  American Indians - 516/million  Asians - 335/million  Caucasians - 268/million USRD 2009

21. USRDS 2012 Report  CKD Prevalence (%) in the NHANES population Overall increase from 12.3% to 14% from 1988-1994 to 2005-2010 Stage 3 CKD increased from 4.9% to 6.7% http://www.usrds.org/atlas.aspx

23. CKD Complications - Anemia

24. Anemia starts early in CKD and worsens with disease progression Kausz AT, et al. Dis Manage Health Outcomes. 2002;10(8):505-513. *Obrador GT, et al. J Am Soc Nephrol. 1999;10:1793-1800

25. Complications of anemia  LVH and other cardiac dysfunction Anemia at any GFR is more likely to be associated with LVH and HF Anemia, independent of GFR, in HF is associated with increased R.R for death Improvement in anemia in CKD was associated with improvement in NYHA functional class  Fatigue  Depression  Reduced exercise tolerance  Increased mortality Silverburg DS Nephrol Dial Transplant 2003; 18(1):141

26. Survival by Anemia and GFR ARIC Study, 1986–2000

27. Target Hemoglobin  Choir Trial – GFR 15-50, starting Hgb. <11.o. Goal 11.3 and 13.5  Create Trial- GFR 15-35. Goal 13-15 or 10.5 -11.5  Treat Trial- Type II DM, GFR 20-60. Goal Hgb. 13  US Normal Hematocrit Trial- ESRD, Baseline 27 to 33. Goal 30 or 42 Hct.

28. Cardiovascular disease mortality in the general population vs. ESRD

29. CKD and Bone Mineral Disorders

30. Vascular Calcification and CKD EBCT Indicating Coronary Calcification Medial Calcification Secondary to CKD London GM, et al. Nephrol Dial Transplant. 2003:18(9):1731-1740

31. CKD and Secondary Hyperparathyroidism in Stage 3-5  High rate of vascular calcification  Treatment Dietary restriction Phosphate binders Vitamin D analogues Cincalcet  No survival advantage demonstrated

32. The Importance of Early Recognition

33. Nephrology CKD Management Hyperlipidemia Smoking

34. Who Should Be Referred (CKD)?  Normal GFR but significant proteinuria, hematuria, or structural abnormalities (solitary kidney, polycystic kidneys).  Stage 3-4 CKD.  Rapid decline in GFR.  Any doubt, better to refer early than wait too long.

35. The Importance of Early Referral  135 patients at Tufts-New England Med Ctr.  Adjusted for any differences in age, race, gender, socioeconomic status, insurance coverage, comorbidities between LR and ER.  LR vs. ER Hypoalbuminemia: 80% vs. 56% Anemia: 55% vs. 33% Hct <28 GFR <5 ml/min/1.73m2 start of HD: 40% vs. 17% Receiving erythropoietin: 17% vs. 40% Functional fistula at start of dialysis: 4% vs. 40% Arora et al. J Am Soc Nephrol 10:1281-1286, 1999.

36. The Importance of Early Recognition  40% of U.S. patients enter Stage 5 CKD (or ESRD) less than 6 months after their initial referral to nephrology.  Missed Opportunities Possible reversible causes Benefits of renoprotection, delaying progression Benefits of cardioprotection Adequate preparation for kidney failure and treatments. Referral for transplantation

37. The Importance of Early Referral  Stark et al., AJKD 2003 Feb;41(2):310-8 2264 patients beginning hemodialysis Dialysis Morbidity and Mortality Study Adjusted mortality risk: late referral (within 4 months of initiation of HD) RR 1.68 (as high as 2.94) compared to patients who saw a nephrologist a year before HD initiation.

38. Types of Hemodialysis Access

41. Preparation of Dialysis  Functional AV fistula at the start of hemodialysis: 4% of late referrals vs. 40% of early referrals.  2011 New York percentage of patients with AV fistula as primary HD access: 62%  KDOQI GOAL: >65%

42. Pros and Cons – AV Fistula  Pros Optimal blood flow rates. Can last the longest. Lowest infection rate. Less likely to clot.  Cons Can take months to mature. Not all patients have adequate vessels. Needles involved. Cosmetics.

44. Pros and Cons – AV Graft  Pros Can be placed in patients with inadequate vessels for an AV fistula. Need less time to “mature,” can be used within 2 to 3 weeks. Better blood flow than a catheter, and properly maintained can last well.  Cons Foreign material (graft) can be infected. More prone to clotting issues than fistula. Needles / cosmetic issues.

45. Pros and Cons of Catheters  Pros Immediately ready to use. No needles.  Cons Low blood flows with more recirculation. Cause stenosis in veins, clot frequently. Infections. Infections

46. The Problems With Catheters  108 patients dialyzing via catheters. 48% had bacteremia by 6 months. Lee T, et al., AJKD 2005 Sep;46(3):501-8.  102 patients dialyzing via catheters 40% had bacteremia requiring catheter removal by 12 months Kieren A, et al., Annals of Int. Med. 1997 Aug; 127(4): 275-80.

47. The Problems With Catheters  66,595 Medicare patients aged 67 or older on dialysis. One year crude death rates: AV fistula 24.9% Synthetic AV graft 28.1% Tunneled catheter 41.5% Xue JL, et al. AJKD 2003 Nov;42(5): 1013-9

48. Fistula vs. Catheter  Compared with arteriovenous fistulas, long term dialysis with tunneled catheters is associated with: 1. Two to threefold increased risk of death 2. Five to tenfold increased risk of infection 3. Increased rate of hospitalization 4. Decreased adequacy of dialysis 5. Increased number of vascular access procedures Rehman R, et al. Clin J Am Soc Nephrol 4: 456-460, 2009.

50. The Importance of Early Recognition Brenner, et al. 2001

51. Relation Between Time of Evaluation and Mortality Among All Patients from Cox Proportional Hazards Regression Analysis Adjusted for modality, demographic factors, SES factors, years smoking, exercise status, comorbidity (ICED), serum albumin, hematocrit, residual GFR. Kinchen KS et al. Annals of Internal Medicine 2002 ;137:479-86