CKD 1-5d
GFR
Stages
Complications
Referral
Access/ESRD
 Thomas Schumacher
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
Estimate of GFR
 Inulin
 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 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
Why not creatinine alone
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
Variations in Serum Creatinine
Increased Serum Creatinine
decreased Serum Creatinine
 Diet
 Aging decreases
 Rhabdomyolysis
production
 Diet
 Decrease muscle mass
 Decreased GFR increases
creatinine secretion
 Nephrotic Syndrome
 Sickle Cell disease
 Medications
Decrease secretion - Trimethoprim,
Dronedarone, Cimetidine,
Ranitidine, Famotidine, Tenofovir,
Interfere with assay - Cefoxitin, Flucytosine
 DKA
 Supplements
Classification of CKD
 NKF – 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)
2)
3)
4)
5)
Hematologic – GFR <30
Cardiovascular – GFR <60
Bone – GFR < 60
Metabolic – GFR < 30
Cognitive
6) HTN
Chronic Kidney Disease Is Progressive
Stages of CKD
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
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 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
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 GFR
ARIC Study, 1986–2000
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.
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 binders
Vitamin 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 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.
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
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.
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 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.
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.
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.
Infections
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.
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
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.
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