CKD 1-5d GFR Stages

ComplicationsReferralAccess/ESRD

Thomas Schumacher

GFRAssessment of functional renal mass

Plot course. Provides prognostic information

Provides no information as to the cause

Need imaging and UA for further information

Estimate of GFRInulin

Scans Iohexol, Iothalamate, TcDTPA,

Creatinine Clearance Cockcroft Gault MDRD CKD EPI 24 hr. urine CrCL

Cystatin C

Why not creatinine?At what level of creatinine does a 65 year-old

diabetic, hypertensive, white woman weighing 50 kg have CKD?

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

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

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

Why not creatinineA 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

Why not creatinine alone

Pitfalls of Creatinine as a marker of GFRCompensatory Hyperfiltration and increased

tubular secretion as GFR decreases

Unrecognized Renal Disease

Steady State?

Age, Race and Body Type

Variations in Serum CreatinineIncreased Serum Creatinine

decreased Serum Creatinine

DietRhabdomyolysisMedications Decrease secretion - Trimethoprim, Dronedarone, Cimetidine, Ranitidine, Famotidine, Tenofovir, Interfere with assay - Cefoxitin, Flucytosine

DKASupplements

Aging decreases production

DietDecrease muscle massDecreased GFR

increases creatinine secretion

Nephrotic SyndromeSickle Cell disease

Classification of CKDNKF – Kidney Disease Outcome Quality

Initiative, (KDOQI ), in 2002

Modified by Kidney Disease Improvement Global Outcome ,(KDIGO).

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 < 60mL/min/1.73m2 for >3 months

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

Chronic Kidney Disease Is Progressive

Stages of CKD

KDIEGOAlbumin 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

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

Incidence of ESRD in US 2005

AA - 991/million

American Indians - 516/million

Asians - 335/million

Caucasians - 268/million

USRD 2009

USRDS 2012 ReportCKD 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

CKD Complications - Anemia

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

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

Survival by Anemia and GFRARIC Study, 1986–2000

Target HemoglobinChoir 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.

Cardiovascular disease mortality in the general population vs. ESRD

CKD and Bone Mineral Disorders

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

CKD and Secondary Hyperparathyroidism in Stage 3-5 High rate of vascular calcification Treatment Dietary restriction

Phosphate bindersVitamin D analogues

Cincalcet No survival advantage demonstrated

The Importance of Early Recognition

Nephrology CKD Management

Hyperlipidemia

Smoking

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.

The Importance of Early Referral135 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.

The Importance of Early Recognition40% 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

The Importance of Early ReferralStark 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.

Types of Hemodialysis Access

Types of Hemodialysis Access

Types of Hemodialysis Access

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%

Pros and Cons – AV FistulaPros 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.

Pros and Cons – AV GraftPros 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.

Pros and Cons of CathetersPros Immediately ready to use. No needles.

Cons Low blood flows with more recirculation. Cause stenosis in veins, clot frequently. Infections. Infections. Infections

The Problems With Catheters108 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.

The Problems With Catheters66,595 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

Fistula vs. CatheterCompared with arteriovenous fistulas, long term

dialysis with tunneled catheters is associated with:1. Two to threefold increased risk of death2. Five to tenfold increased risk of infection3. Increased rate of hospitalization4. Decreased adequacy of dialysis5. Increased number of vascular access

procedures Rehman R, et al. Clin J Am Soc Nephrol 4: 456-460, 2009.

The Importance of Early Recognition

Brenner, et al. 2001

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