Chronic Kidney DiseaseFor the PCM

YOU Can Make a Difference!

CMYuan, 2007

Goals and Objectives

• Review the K/DOQI definition and classification of chronic kidney disease (CKD)

• Review the prevalence and causes of CKD in the US.

• Understand the primary evaluation and management of patients with CKD.

Defining “CKD”

Kidney damage for ≥ 3 months, defined by structural or functional abnormalities of the kidney, with or without decreased GFR, manifest by either Pathologic abnormalities, or Markers of kidney damage, such as abnormalities

of the blood or urine, or in imaging tests (but NOT HTN).

GFR < 60 mL/min/1.73 m2 for ≥ 3 months with or without kidney damage.

Defining “Kidney Damage”

Pathologic Abnormalities? By Radiology (US, CT, MR, etc)--e.g.

Multiple cysts consistent with PKD Extensive scarring Small kidneys--but be careful of the term

“medical renal disease”. REMEMBER: Renal masses or cysts that are

not simple should be referred to a UROLOGIST!!

By Histology--ie, renal biopsy

Defining “Kidney Damage”

Markers of Kidney Damage? Proteinuria Microalbuminuria Hematuria (especially when seen with proteinuria)

Isolated hematuria has a long differential: infection, stone, malignancy, etc.

Casts (especially with cellular elements)

NKF-K/DOQI Stages of “CKD”

Stage Description GFR

(mL/min/1.73m2)

1 Kidney damage with normal or GFR

> 90

2 Mild GFR 60-89

3 Moderate GFR 30-59

4 Severe GFR 15-29

5 Kidney Failure < 15 or dialysis

Primary CareFocus is here!

Prevalence of GFR Categories in the USA(There is a lot of CKD!)

Stage 3 CKD

Prevalence of CKD by GFR in the USA(There is a lot of CKD!)

Stage Description GFR

(mL/min/1.73m2)

Prevalence Prevalence (%)

1 Kidney damage with normal or GFR

> 90 5.9 million 3.3%

2 Mild GFR 60-89 5.3 million 3.0%

3 Moderate GFR 30-59 7.6 million 4.3%

4 Severe GFR 15-29 400,000 0.2%

5 Kidney Failure < 15 or dialysis

300,000 0.2%

Coresh, et al, Am J Kidney Dis. 2003; 41: 1-12

Causes of ESRD in the USA: Prevalent Counts and Adjusted

Rates by Primary Diagnosis

2006 ADR: USRDS

USRDS

Trends in the size of the Medicare CKD population, by diabetic statusFigure 1.1

Patients continuously enrolled in Medicare Part A & Part B in any two consecutive calendar years from 1992 to 2001 (entry period), & alive on the last day of the entry period. Patients enrolled in an HMO or diagnosed with ESRD any time during the entry period are excluded. Estimates of the general Medicare population are based on the 5 percent Medicare sample.

92-93 93-94 94-95 95-96 96-97 97-98 98-99 99-00 00-010

100,000

200,000

300,000

400,000

500,000

600,000

700,000

Diabetic

Non-diabetic

And the numbers are increasing…

Cohort defining Period

CKD Patients Are More Likely to Die than to Progress to ESRD

0% 20%

40%

60%

80%

100%

GFR 60-89, NoProteinuria

GFR 60-89; + Proteinuria

GFR 30-59

GFR 15-29

DiedRRTEvent FreeDisenrolled

Keith, et al, Arch Int Med; 2004; 164:659-663

5 year follow-up

N=27998

The Patient with early stage CKD is 5 to 10 times more

likely to die from a cardiovascular event than

progress to ESRD.

Foley RN, Murray AM, Li S, Herzog CA, McBean AM, Eggers PW, Collins AJ. Chronic kidney disease and the risk for cardiovascular disease, renal replacement, and death in the United States Medicare population, 1998 to 1999. J Am Soc Nephrol 2005; 16:489-95.

So what do we do about this?

Chronic Kidney Disease• In 1999, the NKF approved a proposal for K/DOQI,

Kidney Disease Outcomes Quality Initiative (an evolution of the DOQI (Dialysis Outcomes Quality Initiative).

• The purpose was to develop clinical practice guidelines for the spectrum of kidney diseases.

• In February 2002, Clinical Practice Guidelines for Chronic Kidney Disease (CKD): Evaluation, Classification, and Stratification were published.

Find the KDOQI guidelines atFind the KDOQI guidelines athttp://www.kidney.org/professionals/KDOQI/http://www.kidney.org/professionals/KDOQI/

Guideline 1. Definition and Stages of Chronic Kidney Disease

• Adverse outcomes of CKD can often be prevented or delayed through early detection and treatment. Earlier stages of CKD can be detected through routine laboratory measurements.

• The presence of CKD should be established, based on presence of kidney damage and level of kidney function (glomerular filtration rate [GFR]), irrespective of diagnosis.

• Among patients with CKD, the stage of disease should be assigned based on the level of kidney function, irrespective of diagnosis, according to the K/DOQI CKD classification

Who should we screen?

How should we screen?

Serum Creatinine, CrCl, and eGFR--Serum Creatinine, CrCl, and eGFR--Nothing is Perfect!Nothing is Perfect!

Serum Creatinine alone CAN NOT be used to accurately assess level of kidney function.

S. creatinine is a function of production (muscle mass) and excretion (both GFR and tubular secretion).

Age, sex, and lean body mass have to be taken into account.

Estimations of eGFR (MDRD equation) and CrCl (Cockcroft-Gault equation) were NOT developed in subjects with normal renal function or normal health.

Increase Decrease

Factors Affecting Serum Creatinine Concentration

• Kidney Disease • Ketoacidosis• Ingestion of cooked

meat • Drugs:

– Trimethoprim– Cimetidine– Flucytosine– Some cephalosporins

• Reduced Muscle Mass

• Malnutrition

Remember….GFR normally decreases with age!

Cockcroft-Gault Equation to Predict GFR

• Developed to predict creatinine clearance, thus an overestimate of GFR

• Prediction based on age, gender, creatinine and ideal body weight

• ClCr (cc/min) = [140-age] x IBW/72 x SCr x [0.85 if female]

• Used almost universally as the basis for drug dosing!

Get it athttp://www.kidney.org/professionals/KDOQI/gfr.cfm

MDRD Equation to Predict GFR

• Prediction based on age, gender, race and serum creatinine. Developed to follow GFR as part of the Modification of Diet in Renal Disease (MDRD) study. Validated.

• GFR/1.73m2 = 186 x [Pcr]-1.154 x [age]-0.203 x [0.742 if female] x [1.212 if AfAm]

TA-DA!(Your on-line link to the MDRD GFR

calculator)

http://www.kidney.org/professionals/KDOQI/gfr.cfm

Cockcroft-Gault vs. MDRD

The MDRD equation estimates The MDRD equation estimates GFR.GFR. eGFR is given per 1.73meGFR is given per 1.73m22 BSA BSA

The Cockcroft-Gault equation estimates The Cockcroft-Gault equation estimates CrCl.CrCl. CrCl is best used for drug dosing CrCl is best used for drug dosing

decisions--drug dosing is usually indexed decisions--drug dosing is usually indexed to CrCl.to CrCl.

Comparing the Cockcroft-Gault and MDRD:Do these patients have the same level of renal

function?

• 20 year old AfAm Washington Redskins tackle, weighing 144 kg with a SCr 1.2 mg/dl?

ClCr=[140-20][144]/72 x [1.2] =200 cc/min

• 93 year old Caucasian female nursing home resident, weighing

44 kg with a SCr 1.2 mg/dl.

ClCr = [140-93][44]/72 x [1.2] x 0.85 = 20 cc/min

MDRD GFR Value:99 mL/min/1.73 m2

MDRD GFR Value:45 mL/min/1.73 m2

YES NO

Risk Factor ReductionDetermine Stage of CKD Determine underlying cause Identify risk factors for progression Identify comorbidites

Patient meets definition of Chronic Kidney Disease?

Tools for Determining the Cause of Chronic Kidney Disease

• CKD is often silent. Assessment relies on laboratory testing and imaging.

• A Good History! ROS, existence of chronic diseases (DM, HTN, CHF, cirrhosis), medication review, accurate PMH and FH of kidney disease.

• Helpful Physical Examination! BP, evidence of co-morbid conditions and complications of CKD.

A Simple Laboratory Evaluation!

Simplified Classification of CKD by Diagnosis

• Diabetic Kidney Disease

• Nondiabetic Kidney Disease • Glomerular disease

– autoimmune, sytemic infections, drugs, neoplasia, idiopathic

• Vascular disease – ischemic renal disease,

hypertensive nephrosclerosis, microangiopathy

• Tubulointerstitial disease – UTO, stones, UTI, drug toxicity

• Cystic disease• Post-Transplant

Differential Diagnosis of Chronic Kidney Disease

• Everyone deserves a diagnosis! • This is especially true for Stage 1 or 2 CKD!• When in doubt, consult a nephrologist!• Initial evaluation will guide further diagnostics,

decisions about renal biopsy and often decisions about treatment and prognosis.

So Now What Do You Do? (There’s a lot you can do!)

CKD Clinical Action Plan On-Line

http://www.kidney.org/professionals/kdoqi/cap/index.html

Primary Goals of CKD Care

• To prevent cardiovascular events and death• Heart Attacks• Congestive Heart Failure• Sudden Cardiac Death• Stroke

• To prevent the progression of CKD to Kidney Failure or ESRD

• To prevent complications of CKD• To prepare for dialysis/transplantation in a timely

manner

Clinical Action Plan• A Clinical Action Plan should be developed for each patient,

based on the stage of CKD (see Table 33).• Patients with CKD should be evaluated to determine:

– Diagnosis– Comorbid Conditions– Severity, assessed by level of kidney function– Complications, related to level of kidney function– Risk for loss of kidney function– Risk for cardiovascular disease

• Review of medications should be performed at all visits.• Self-management behaviors should be incorporated into the

treatment plan at all stages of chronic kidney disease.

Management of Patients with Chronic Kidney Disease

B lood g lu cose con tro l

B P C on tro l

A R B s

A C E In h ib ito rs

In te rven tion s th a t d e lay p rog ress ion

R ed u ced F u n c tion in g an d W e ll-b e in g

M a ln u trit ion

O s teod ys trop h y

A n em ia

P reven tion o f U rem ic C om p lica tion s(G F R < 6 0 cc /m in /1 .7 3 m 2 )

C ard iovascu la r D isease

M od ifca tion o f C om orb id ity

P re -em p tive Tran sp lan ta tion

K id n ey Tran sp lan t E va lu a tion

T im e ly D ia lys is In it ia tion

T im e ly D ia lys is A ccess P lacem en t

C h o ice o f D ia lys is M od a lity

E d u ca tionA n "E S R D C lin ic "

P rep ara tion fo r R en a l R ep lacem en t Th erap y(G R F < 3 0 cc /m in /1 .7 3 m 2 )

E arly D e tec tion o f C K D

RENAL INJURY

Reduction in nephron mass

Glomerular capillary hypertension

Increased glomerular permeability

to macromolecules

Increased filtration of plasma proteinsProteinuria

Excessive tubular protein reabsorption

Tubulointerstitial inflammation

RENAL SCARRING

PROGRESSIVE RENAL DAMAGE:

The Final Common Pathway

Increased BP

Nonmodifiable Modifiable

Patient characteristics associated with increased rate of GFR decline

• African American race

• Male gender • Older age• Lower baseline level

of kidney function

• Higher level of proteinuria

• Higher BP • Poor glycemic

control • Smoking

GUIDELINE 13. LOSS OF KIDNEY FUNCTION IN CKD Interventions to slow the progression should be considered in all patients with CKD

Interventions proven to be effective include: 1. Strict glucose control in diabetes; 2. Strict blood pressure control; 3. ACEI and ARBs

Interventions that may be effective, but studies are inconclusive, include: • Dietary protein restriction; • Lipid-lowering therapy; • Partial correction of anemia.

Attempts should be made to prevent acute renal failure: •Volume depletion; •IV contrast; •Some antibiotics (for example, aminoglycosides and amphotericin B); •NSAIDs, including COX 2 inhibitors; •Other drugs: ACEI, ARBs, calcineurin inhibitors •Obstruction.

eGFR should be obtained at least yearly in CKD, and more often in patients with: •GFR <60 mL/min/1.73 m2; •Fast GFR decline in the past •Risk factors for faster progression; •Ongoing treatment to slow progression; •Exposure to risk factors for acute GFR decline.

Slowing ProgressionThe Earlier, the Better…

Interventions that delay progression of CKD: ACEI and ARBs

• Mechanisms – Lower systemic blood pressure – Lower glomerular capillary blood pressure and

protein filtration– Reduce AT II mediated cell proliferation and

fibrosis

Should be employed in all proteinuric kidney diseases!

Measuring Proteinuria—Get into the right spot!

When you get to this point,Don’t continue to get microalbumin!

RENAL INJURY

Reduction in nephron mass

Glomerular capillary hypertension

Increased glomerular permeability

to macromolecules

Increased filtration of plasma proteinsProteinuria

Excessive tubular protein reabsorption

Tubulointerstitial inflammation

RENAL SCARRING

PROGRESSIVE RENAL DAMAGE:

The Final Common Pathway

Increased BP ACEI ARB

ACEI ARB

ACEI ARB

Interventions that delay progression of CKD: ACEI and ARBs

• Diabetic Kidney Disease – ACEI or ARB in all diabetic patients with microalbuminuria– ACEI (alt ARB) for Type 1 Diabetics with macroalbuminuria– ARB (alt. ACEI) in Type 2 Diabetics with macroalbuminuria

• Nondiabetic Kidney Disease – ACEI/ARB recommended in all proteinuric (>200 mg/g Cr on

spot urine) patients with CKD– May tolerate creatinine rise of 35% above baseline– <130/80 is goal– 3 or more drugs may be required! One will probably be a

diuretic (thiazide first, then loop)– ACEI and ARB may be used in combination

-KDOQI Guideline 8, Table 110-JNC 7, 2003 http://www.nhlbi.nih.gov/guidelines/hypertension/express.pdf

-HTN is both a cause and a complication of CKD. -HTN may develop early during the course of CKD and is associated with adverse outcomes—in particular, faster loss of kidney function and development of CVD. -Blood pressure should be closely monitored in all patients with chronic kidney disease.-Treatment of high blood pressure in CKD should include specification of target BP levels, nonpharmacologic therapy, and specific antihypertensive agents for the prevention of progression of kidney disease and development of cardiovascular disease.

Controlling HypertensionGUIDELINE 7. ASSOCIATION OF LEVEL OF GFR WITH

HYPERTENSION

Pathogenic Mechanisms of High Blood Pressure in CKD

• Pre-existing essential hypertension • Extracellular fluid volume expansion • Renin-agniotensin aldosterone system stimulation • Increased sympathetic activity • Alteration in endothelium-derived factors(NO/endothelin) • Increased body weight • Erythropoietin administration • PTH secretion/hypercalcemia • calcified arterial tree • renal vascular disease and renal artery stenosis

Relationship between BP and progression of diabetic nephropathy.

BP, albumin excretion rate, and GFR in patients with type 1 DMs randomly assigned to a reduction in MAP of 10 mm Hg using metoprolol at 100 to 400 mg/d, hydralazine at 50 to 200 mg/d, and furosemide at 80 to 500 mg/d versus no antihypertensive therapy. Solid circles represent the treated group. Open circles represent the control group. Vertical lines represent standard error. Study was stopped earlier in the control group because of faster decline in GFR. Reprinted with permission.253

BP vs. Time

Controls

AER vs. Time GFR vs. Time

Controls

Controls

Controls

Relationship between MAP and GFR decline (Non-diabetic Pts).

Mean GFR decline and achieved follow-up BP in MDRD Study A (patients with baseline GFR 25 to 55 mL/min/1.73 m2). Regression lines relating the estimated mean GFR decline over 3 years to mean follow-up MAP for groups of patients defined according to baseline proteinuria. Within each group, a 3-slope model was used with break points at 92 and 98 mm Hg. Reprinted with permission.255

“Nephrotic”

JNC-7 recommends a goal blood pressure of <130/80 mm Hg for individuals with high blood

pressure and CKD.

http://www.nhlbi.nih.gov/guidelines/hypertension/express.pdf

Population BP Goal Nondrug Rx Drug RX

CKD + >200mg/g <130/80 Reduce salt ACEI/ARBProt/Cr Ratio BMI≤25 kg/m2 Then diuretic

Mod EtOH Then BB or CCBStop SmokingExercise

CKD + no proteinuria <130/80 Same Thiazide/LoopThen ACEI/ARBThen BB or CCB

Recommendations for Controlling HTN in Non-Diabetic CKD

KDOQI Table 118, Guideline 9

Interventions that delay progression of CKD: Strict Glycemic Control

• 80% Type I DM with microalbuminuria develop DN in 10-15years, 50% to ESRD – DCCT, benefit of tight control in reducing

occurrence subclinical and overt DN(40-60%)

• 20-40% Type II DM with microalbuminuria develop DN, 20% to ESRD – UKPDS 33, 25% reduction in microvascular

events– Kumamoto – Steno Type 2, 73% reduction in clinical proteinuria

Interventions that delay progression of CKD: Strict Glycemic Control

Recommended Therapy:

• HgbA1c < 7%

• Additional information in 2001 ADA Clinical Practice Guidelines www.diabetes.org/clinicalrecommendations/

Supplement101/S3.htm

Management of Patients with Chronic Kidney Disease

B lood g lu cose con tro l

B P C on tro l

A R B s

A C E In h ib ito rs

In te rven tion s th a t d e lay p rog ress ion

R ed u ced F u n c tion in g an d W e ll-b e in g

M a ln u trit ion

O s teod ys trop h y

A n em ia

P reven tion o f U rem ic C om p lica tion s(G F R < 6 0 cc /m in /1 .7 3 m 2 )

C ard iovascu la r D isease

M od ifca tion o f C om orb id ity

P re -em p tive Tran sp lan ta tion

K id n ey Tran sp lan t E va lu a tion

T im e ly D ia lys is In it ia tion

T im e ly D ia lys is A ccess P lacem en t

C h o ice o f D ia lys is M od a lity

E d u ca tionA n "E S R D C lin ic "

P rep ara tion fo r R en a l R ep lacem en t Th erap y(G R F < 3 0 cc /m in /1 .7 3 m 2 )

E arly D e tec tion o f C K D

When to Expect Complications…

Anemia and CKDAnemia and CKD• Anemia usually develops during the course of chronic

kidney disease and may be associated with adverse outcomes.

• Anemia is one of the modifiable complications of CKD.• All individuals with hemoglobin (Hb) levels lower than physiologic

norms are considered anemic. Erythropoietin deficiency is the primary cause of anemia of CKD. The NKF recommends that evaluation for anemia should occur

when GFR <60 mL/min/1.73 m2; measurement should include Hb level.

Anemia should be treated according to the K/DOQITM guidelines for anemia of CKD.

K/DOQI: K/DOQI: Evaluation and Management Evaluation and Management of Anemiaof Anemia

For Adults with ≥ Stage 3 CKD: Assess Hemoglobin level If anemia (HgB ≤ 12)

RBC indices/CBC Reticulocyte count Iron studies Test for occult GI bleeding as indicated Medical evaluation of comorbid conditions

Erythropoetin levels are usually NOT indicated.

Prevention of Uremic Complications:Anemia Therapy

• Subcutaneous administration of erythropoietin once to thrice weekly (sometimes less).

• Supplemental oral or IV iron to keep ferritin > 100 and iron saturation >20%.

• Monthly monitoring of Hgb, iron stores.• Monthly adjustments in EPO dose and

frequency to meet target Hgb 11-12 g/dl (HCT 33-36%).

•Bone disease and disorders of calcium and phosphorus metabolism develop during the course of chronic kidney disease and are associated with adverse outcomes.

-Patients with GFR <60 mL/min/1.73 m2 should be evaluated for bone disease and disorders of calcium and phosphorus metabolism.-Patients with bone disease and disorders of bone metabolism should be evaluated and treated—see K/DOQI Clinical Practice Guidelines on Bone Metabolism and Disease in Chronic Kidney Disease (October, 2004).

GUIDELINE 10. ASSOCIATION OF LEVEL OF GFR WITH BONE DISEASE AND DISORDERS OF CALCIUM AND

PHOSPHORUS METABOLISM

Prevention of Uremic Complications:Osteodystrophy

• Osteitis fibrosis cystica, due to 2o HPT, is major form of bone disease.

• Check indices of bone and mineral metabolism at GFR < 60 cc/min/1.73m2:

– iPTH the earliest marker– Hypocalcemia, hyperphosphatemia – Phosphorus control is cornerstone of treatment

Prevention of Uremic Complications:Osteodystrophy Therapy

• Restrict dietary phosphorus to 800-1,000 mg/d

• Calcium-based phosphate binders (but not with Vit D!) to combat hypocalcemia and bind phosphorus

• Assure repletion of Vitamin D 25 • Avoid acidosis, HCO3> 23 mEq/l

Management of Renal

Osteodystrophy is Very

Complex!

http://www.kidney.org/professionals/KDOQI/

guidelines_bone/index.htm

•Protein energy malnutrition develops during the course of chronic kidney disease and is associated with adverse outcomes. Low protein and calorie intake is an important cause of malnutrition in chronic kidney disease.

•Patients with GFR <60 mL/min/1.73 m2 should undergo assessment of dietary protein and energy intake and nutritional status:

•Guideline 23. Panels of Nutritional Measures for Nondialyzed Patients: "For individuals with CRF (GFR <20 mL/min) protein-energy nutritional status should be evaluated by serial measurements of a panel of markers including at least one value from each of the following clusters:

(1) Serum albumin; (2) Edema-free actual body weight, percent standard (NHANES II) body weight, or subjective global assessment (SGA); and (3) Normalized protein nitrogen appearance (nPNA) or dietary interviews and diaries. (Evidence and Opinion)"

•Guideline 26. Intensive Nutritional Counseling for Chronic Renal Failure: "The nutritional status of individuals with CRF should be monitored at regular intervals."

GUIDELINE 9. ASSOCIATION OF LEVEL OF GFR WITH NUTRITIONAL STATUS

Prevention of Uremic Complications:Malnutrition

• Contributors to protein-energy malnutrition(PEM) in CKD: – low protein and calorie intake – metabolic acidosis – resistance to insulin, GH, IGF-1 – proinflammatory cytokines

• Assessment of nutritional status requires multiple markers to assess protein status, fat stores, body composition and dietary protein and energy intake.

Prevention of Uremic Complications:Nutrition Guidelines

• Protein intake – 0.75g/kg/d (RDA) – GFR < 25 cc/min(Stages 4-5) consider 0.6g/kg/d

• Energy intake – RDA depends on energy expenditure – GFR < 25 cc/min(Stages 4-5) 30-35kcal/kg/d

• Patients with less than recommended intake need frequent follow-up of nutritional status

Prevention of Uremic Complications:Just a Word About Immunizations

• Don’t forget to continue routine immunizations, e.g.– Tetanus– Pneumococcus– Influenza

• Hepatitis B – Check for immunity first--ie, hepatitis B sAb, sAg, cAb – Those who are immune or have chronic infection do not

need the vaccine.– All others should receive the vaccine. Don’t wait for dialysis!

Patients with advanced chronic kidney disease are less likely to gain immunity from the vaccine. Consider for all Stage 3 or greater CKD patients!

Management of Patients with Chronic Kidney Disease

B lood g lu cose con tro l

B P C on tro l

A R B s

A C E In h ib ito rs

In te rven tion s th a t d e lay p rog ress ion

R ed u ced F u n c tion in g an d W e ll-b e in g

M a ln u trit ion

O s teod ys trop h y

A n em ia

P reven tion o f U rem ic C om p lica tion s(G F R < 6 0 cc /m in /1 .7 3 m 2 )

C ard iovascu la r D isease

M od ifca tion o f C om orb id ity

P re -em p tive Tran sp lan ta tion

K id n ey Tran sp lan t E va lu a tion

T im e ly D ia lys is In it ia tion

T im e ly D ia lys is A ccess P lacem en t

C h o ice o f D ia lys is M od a lity

E d u ca tionA n "E S R D C lin ic "

P rep ara tion fo r R en a l R ep lacem en t Th erap y(G R F < 3 0 cc /m in /1 .7 3 m 2 )

E arly D e tec tion o f C K D

Patients with CKD, irrespective of diagnosis, are at increased risk of cardiovascular disease (CVD), including coronary heart disease, cerebrovascular disease, peripheral vascular disease, and heart failure. Both “traditional” and “chronic kidney disease related (nontraditional)” CVD risk factors may contribute to this increased risk.

-All patients with CKD should be considered in the “highest risk” group for CVD, irrespective of levels of traditional CVD risk factors.-All patients with CKD should undergo assessment of CVD risk factors, including:

•Measurement of “traditional” CVD risk factors in all patients; •Individual decision-making regarding measurement of selected “CKD-related” CVD risk factors in some patients.

-Recommendations for CVD risk factor reduction should take into account the “highest-risk” status of patients with chronic kidney disease.

GUIDELINE 15. ASSOCIATION OF CHRONIC KIDNEY DISEASE WITH CARDIOVASCULAR DISEASE

The most common cause of death among ESRD patients is CVD

Fig 5. Causes of death among period prevalent patients 1997–1999, treated with hemodialysis, peritoneal dialysis, or kidney transplantation. Data are from

the USRDS 2001 Annual Data Report (www.usrds.org). Abbreviations: MI, myocardial infarction; HD, heart disease.

Modification of Comorbidity:Cardiovascular Disease

• CVD is the cause of death in 40-50% ESRD patients

• ESRD CVD mortality rates 15x higher than general population.

• CVD is leading cause of death in patients with CKD, regardless of stage. – HDFP, pts with Cr> 1.7mg/dl, 58% deaths CV – British Regional Heart Study, 50% deaths CV in

patients in upper decile of baseline Cr

GFR and relative risk for CVD-related death. Wannamethee625: risk is for SCr 1.5 mg% vs SCr 1.3 mg%. Culleton622: risk is for SCr

1.5 mg% and 1.4 mg% vs. <1.5 and <1.4 in men and women respectively. Upper limit for SCr was 3.0 mg%. Mann637: risk is for SC  1.4 mg% vs <1.4 mg%. Ruilope634:

risk is for SCr >1.5 mg% vs 1.5 mg%. Upper limit for SCr was 3.0 mg%. Fried640: risk is

for SCr 1.5 mg% versus SCr 0.9 mg%. Hemmelgarn642: risk is for SCr >2.3 mg/dL vs

2.3 mg/dL.

Proteinuria and relative risk for cardiovascular disease. Where possible, results presented are from multivariable analyses. Agewall650, Ljungman647: Unadjusted results shown. Data not available to calculate age or multivariable adjusted risk.

Modification of Comorbidity:Cardiovascular Disease

• Patients with CKD should be considered highest risk for CVD.

• Aggressive intervention and management of traditional CV risk factors is indicated.

• This particularly includes dyslipidemias.– All adults with Stage1-5 CKD should be evaluated

for dyslipidemia.– Fasting lipid profile with total cholesterol, LDL,

HDL and triglycerides, at baseline, and at least annually.

Management of Dyslipidemia in CKD

Expert Panel on Detection Evaluation and Treatment of High Blood Cholesterol in Adults. Executive Summary of the Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). JAMA, 2001, 285;2486-2497.

http://www.kidney.org/professionals/KDOQI/guidelines_lipids/index.htm

Management of Patients with Chronic Kidney Disease

B lood g lu cose con tro l

B P C on tro l

A R B s

A C E In h ib ito rs

In te rven tion s th a t d e lay p rog ress ion

R ed u ced F u n c tion in g an d W e ll-b e in g

M a ln u trit ion

O s teod ys trop h y

A n em ia

P reven tion o f U rem ic C om p lica tion s(G F R < 6 0 cc /m in /1 .7 3 m 2 )

C ard iovascu la r D isease

M od ifca tion o f C om orb id ity

P re -em p tive Tran sp lan ta tion

K id n ey Tran sp lan t E va lu a tion

T im e ly D ia lys is In it ia tion

T im e ly D ia lys is A ccess P lacem en t

C h o ice o f D ia lys is M od a lity

E d u ca tionA n "E S R D C lin ic "

P rep ara tion fo r R en a l R ep lacem en t Th erap y(G R F < 3 0 cc /m in /1 .7 3 m 2 )

E arly D e tec tion o f C K D

When to Refer!

• Consider co-management with a nephrologist if the clinical action plan cannot be carried out.

• Consider subspecialty referral when*: – Unexplained proteinuria (>1gm/day) or microalbumin/Cr ratio

>250mg albumin/gCr– Unexplained macroscopic or microscopic hematuria– Diabetes and macroalbuminuria– Multiple and recurring kidney stones– Rapidly deteriorating kidney function– Difficult to control hypertension

• Refer to a nephrologist when GFR <30 mL/min/1.73 m2 (CKD Stages 4-5)!

Mandatory Referral to Nephrologist guideline, Niagara Health Quality Coalition, NY

Fig 11. Level of GFR at initiation of replacement therapy (USRDS). Data from Obrador et al.77

DiabeticsMedicare EligibleMost should have started

Preparation for Renal Replacement Therapy

(GFR < 30cc/min/1.73m2)

• Referral to a Nephrologist allows: – Early identification of RRT modality. – Evaluation for kidney transplantation with goal of

pre-emptive transplantation. – REMEMBER, in eligible patients transplantation

confers a survival advantage over dialysis!– Identification of social, functional or nutritional

needs.

Preparation for Renal Replacement Therapy

(GFR < 30cc/min/1.73m2)

• Close coordination between PCM and nephrologist allows:– Timely placement of dialysis access– Timely initiation of dialysis– Timely referral for transplant evaluation

with preemptive transplant if possible.

Conclusions

• CKD is a public health problem with poor outcomes and high cost. CKD is underdiagnosed and undertreated in the U.S.

• Early CKD detection and intervention may increase opportunities for the prevention of ESRD and of complications of CKD, including death.

YOU, the PCM, CAN MAKE A Difference!