current state of management in primary care. jayant kumar, md · - jafar, et al., 2001 • blood...

12/04/2013

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Chronic Kidney Disease

Current state of management in Primary Care.

Jayant Kumar, MDRenal Medicine Assoc., Albuquerque, NM

Definition ofChronic Kidney Disease

AJKD 2002: 39(2)

Stages of Chronic Kidney Disease

AJKD 2002: 39(2)

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USRDS ADR, 2007

Prevalence of ESRD has been rising steadily

Awareness of Early-Stage CKD Is Low in the US Population

*Proportion of patients who were told they had weak or failing kidneys, eGFR (mL/min/1.73 m2). Coresh et al. J Am Soc Nephrol. 2005:16:180-188.

<30 30+ <30 30+ <30 30+ F MSex:Albuminuria:

eGFR: 90+ 60-89 30-59 30-59

© 2005 The Johns Hopkins University School of Medicine.

USRDS ADR, 2007

Diabetes and hypertension are leading causes of kidney failure

Incident ESRD rates, by primary diagnosis, adjusted for age, gender, & race.

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AJKD 2002: 39(2)

Why Estimate GFR From SCr, Instead of Using SCr for Kidney Function?

*B = black; †W = all ethnic groups other than black. GFR calculator available at: www.kidney.org/index.cfm?index=professionals. Accessed 3/28/05.

Age Gender RaceSCr

(mg/dL)eGFR (mL/min/1.73

m2) CKD Stage

20 M B* 1.3 91 1

20 M W† 1.3 75 2

55 M W 1.3 61 2

20 F W 1.3 56 3

55 F B 1.3 55 3

50 F W 1.3 46 3

Stages of CKD: A Clinical Action Plan

AJKD 2002: 39(2)

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Incident ESRD patients; rates adjusted for age & gender.

Incidence varies widely by race and ethnicity

Rat

e p

er m

illio

n p

op

ula

tio

n

Af Am

N AmHispanicAsian

WhiteNon-Hispanic

USRDS ADR, 2007

Diabetes (DM) and hypertension (HTN) often coexist in CKD

USRDS ADR, 2006

Distribution of CKD, HTN, & diabetic patients in Medicare population, 2004.

USRDS ADR, 2006

CKD is disproportionately costly

Distribution of costs for CKD, HTN, & diabetic patients in Medicare population, 2004.

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26 million Americans have CKD or albuminuria

Coresh, et al., 2007

But few are aware of it – even those with eGFR less than 30

Coresh, et al., 2007

CKD is prevalent in CVD

Ix, et al., 2003; Anavekar, et al., 2004; Shlipak, et al., 2004.

CADCrCl ≤60 mL/min

AMI

GFR <60 mL/min

CHF

GFR ≤60 mL/min

23%

46%

33%

Pa

tie

nts

Wit

h C

KD

(%

)

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In addition to ESRD, CKD leads to CVD

Go, et al., 2004

Ad

just

ed

Ha

zard

Ra

tio

eGFR

Adjusted* hazard ratio for CVD events

People with CKD do progress to kidney failure–especially those middle-aged and younger

Levey, et al., 2006

Long term (7 year) follow up of 408 non-diabetic CKD patients (mean initial GFR=39, mean initial age=52 year old)

Younger people with CKD are more likely to develop ESRD before death

Copyright ©2007 American Society of NephrologyO'Hare, 2006

Annual mortality by age group and eGFR.

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• Intensive glycemic control lessens progression from microalbuminuria in Type 1 diabetes–goal in Type 2 is less clear- DCCT, 1993

- ACCORD, 2008

• Antihypertensive therapy with ACE Inhibitors or ARBs lessens proteinuria and progression- Giatras, et al., 1997- Psait, et al., 2000- Jafar, et al., 2001

• Blood pressure below 130/80 is beneficial- Sarnak, et al., 2005

We can have an impact on progression of CKD

Incidence of ESRD has leveled off, perhaps because of better use of preventive measures

Incident ESRD patients; rates adjusted for age, gender & race.

Rat

e p

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illio

n p

op

ula

tio

n

USRDS ADR, 2007

Adherence to treatment guidelines –room for improvement

The percentage of diabetic CKD patients receiving ACE-Is/ARBs has been slow to improve

Per

cen

t o

f p

atie

nts

USRDS ADR, 2007

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2 simple tests will identify CKD in adults

• eGFR - Estimated GFR from serum creatinine using the MDRD equation

• UACR - Urine albumin to creatinine ratio on a “spot” urine sample

• 24-hour urine collections are NOT needed

- Diabetics should be tested once a year. Others at risk can be tested less frequently as long as normal.

• MDRD estimating equation is not applicable to children

• Updated Schwartz formula provides reasonable estimate in children with mild-moderate CKD

(GFR – 15-75 mL/min/1.73 m2)

Updated Schwartz Formula

eGFR = k * Ht/Scr

Where k=0.4, Ht in cm and Scr in mg/dL and measured by enzymatic methodology

Estimation of GFR in children

Caveats to eGFR

• An estimate based on population data--not the patient’s actual GFR

• Not reliable when used with patients:

– with GFR above 60 ml/ min/1.73 m2

– with rapidly changing creatinine levels (e.g., acute renal failure in the ICU)

– with extremes in muscle mass, e.g. cachexia or paraplegia

– under age 18

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Diabetes

The Leading Cause of Kidney Failure

Increased Mortality in Patients With Diabetes and CKD: 2-Year Clinical Outcomes

CKD identified as ICD-9-CM diagnosis code, includes CKD from diabetes, hypertension, obstructive uropathy, and other diagnosis codes reported on USRDS ESRD registration forms.DM = diabetes mellitus; ESRD = end-stage renal disease; ICD-9-CM = International Statistical Classification of Diseases, 9th Revision, Clinical Modification.Collins et al. Kidney Int. 2003;64(suppl 87):S24-S31.

+ DM, - CKD

- DM,+CKD

+ DM,+ CKD

Medical Cohort

Pat

ien

ts (

%)

0

20

40

60

80

100

84.067.6 61.6

No Events

29.515.7

32.3

DeathESRD, CKD Stage 5

0.3

2.96.1


Proteinuria Predicts Stroke and CHD Events in Patients With Type 2 Diabetes

P<0.001

40

30

20

10

0Stroke CHD

Events80604020

0

0.5

0.6

0.7

0.8

0.9

1.0

Su

rviv

al C

urv

es f

or

CV

Mo

rtal

ity

Overall: P<0.001

Inci

den

ce (

%)

Follow-Up (mo)

CHD = coronary heart disease; Prot = urinary protein excretion; CV = cardiovascular.Miettinen et al. Stroke. 1996;27:2033-2039.

Prot 150-300 mg/LProt <150 mg/L Prot >300 mg/L

0 100


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lb1 slide 9 How was this study done? How many people included; what levels of CKDL. Blonde, 08/04/2005

Slide 27

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Evidence for Effects of Good Glycemic Control on Complications, Including Nephropathy

DCCT = The Diabetes Control and Complications Trial.DCCT Study Group. N Engl J Med. 1993;329:977-986; Ohkubo. Diabetes Res Clin Prac. 1995;28:103-117; UKPDS Study Group. Lancet. 1998;352:837-853.

Trial

Complication

DCCTA1C: (9 7%)

N = 1441

Kumamoto(9 7%)N = 110

UKPDS(8 7%)N = 5102

Retinopathy 76% 69% 17-21%

Nephropathy 54% 70% 24-33%

Neuropathy 60% – –


Hypertension

The Second Leading cause of Kidney Failure

Recommendations for BP and RAS Management in CKD

BP = blood pressure; RAS = renin angiotensin system; CCB = calcium channel blocker; BB = -blocker; JNC 7 = The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure.ADA. Diabetes Care. 2005;28(suppl 1); Chobanian et al. JAMA. 2003;289:2560-2572; Kidney Disease Outcomes Quality Initiatives (K/DOQI). Am J Kidney Dis. 2004;43(5 suppl 1):S1-S290.

PatientGroup

Goal BP(mm Hg) First Line Adjunctive

+ Diabetes <130/80 ACE-I or ARB Diuretics then CCB or BB

Diabetes + Proteinuria

<130/80 ACE-I or ARB Diuretics then CCB or BB

Diabetes Proteinuria

<130/80 No specific preference:

Diuretics then ACE-I, ARB, CCB, or BB

EXPECT TO NEED TO USE 3+ AGENTS TO ACHIEVE GOALSRecommendations largely consistent across JNC 7, ADA, and K/DOQI


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ACEI/ARB & Reduced Risk of Rapid GFR Decline, Kidney Failure, or Death

Wright et al for the AASK Study Group. JAMA. 2002;288:2421-2431. [AASK - African American Study of Kidney Disease and Hypertension]Brenner et al for the RENAAL Study Investigators. N Engl J Med. 2001;345:861-869. [RENAAL = Reduction of Endpoints in NIDDM with the Angiotensin II Antagonist Losartan]Lewis et al for the Collaborative Study Group. N Engl J Med. 2001;345:851-860.[IDNT = Irbesartan in Diabetic Nephropathy Trial.]

Ramipril vs Amlodipine

P = 0.004

Ramipril vs Metoprolol

P = 0.04

Losartan vs Placebo P = 0.02

-38

-22

-16

Irbesartan vs Placebo

P = 0.02

-20

Irbesartan vs Amlodipine

P = 0.006

-23

AASK (N=1094) RENAAL (N=1513) IDNT (N=1722)


Relationship Between Achieved BP and GFR

MAP = Mean Arterial Pressure*

r = 0.69P<0.05

UntreatedHypertension

130/80 140/90

*MAP = [SBP + (2 × DBP)]/3 mm Hg.Summary of 9 studies used in figure.Parving et al. 1989; Viberti et al. 1993; Klahr et al. 1993; Hebert et al. 1994; Lebovitz et al. 1994; Moschio et al. 1996; Bakris et al. 1996; Bakris et al. 1997; GISEN Group. 1997.Bakris et al. Am J Kidney Dis. 2000;36:646-661.


Anemia

Close association with CKD stage

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*NHANES participants aged ≥20 y with anemia as defined by WHO criteria: hemoglobin (Hgb) <12 g/dL for women, and Hgb <13 g/dL for men. USRDS 2004 Annual Data Report. The data reported here have been supplied by the USRDS. The interpretation and reporting of these data are the responsibility of the author(s) and in no way should be seen as an official policy or interpretation of the U.S. government. Available at: www.usrds.org. Accessed 3/28/05.

Anemia Prevalence by CKD Stage

Pat

ien

ts W

ith

An

emia

* (%

)

NHANES IIINHANES 1999-2000

CKD Stage


Anemia Treatment Eligibility

Serum Creatinine (2.0 mg/dl or above) or

Creatinine Clearance (45 ml/min or below) and

Hemoglobin (10g/dl or below) or

Hematocrit (30% or below) or

Symptoms of anemia

Consequences of Anemia in CKD Reduced oxygen delivery to tissues

Decrease in Hgb compensated by increased cardiac output

Progressive cardiac damage and progressive renal damage1

Increased mortality risk2

Reduced quality of life (QOL)3

Fatigue

Diminished exercise capacity

Reduced cognitive function Left ventricular hypertrophy (LVH)4

1. Silverberg et al. Blood Purif. 2003;21:124-130. 2. Collins et al. Semin Nephrol. 2000;20:345-349; 3. The US Recombinant Human Erythropoietin Study Group. Am J Kidney Dis. 1991;18:50-59; 4. Levin. Semin Dial.2003;16:101-105.


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Impact of treatment

Risk of ESA use includes increase cardio-vascular events like MI/Stroke, worsening HTN and progression of solid tumors

Maximize iron stores before using ESA

Read the FDA black box warning and consent patients before ESA use

ESA use and correction of Hb above 10 decreases transfusion need and hence better chance to get kidney transplant

Secondary Hyperparathyroidism

An Early and Modifiable Complication of CKD

Calcitriol Decline and iPTH Elevation as CKD Progresses

N = 150.iPTH = intact PTH. Adapted from Martinez et al. Nephrol Dial Transplant. 1996;11(suppl 3):22-28.

eGFR (mL/min/1.73 m2)

152535455565758595105

100

200

300

400

0

10

20

30

40

50

iPT

H(p

g/m

L)

Cal

citr

iol

1,25

(OH

) 2D

3(p

g/m

L)

Stage 37.4 million

Stage 25.7 million

Stage 4300,000

CKD Stage 15.6 million

25

65

Low-Normal

Calcitriol

High-Normal PTH


QE1 M236_1708 Thadhani CDTitle changedQED Employee, 08/03/2005

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Feedback Loops in SHPT

Ca = calcium; CVD = cardiovascular disease; P = phosphorus.Courtesy of Kevin Martin, MB, BCh.

PTH

Bone DiseaseFracturesBone pain

Marrow fibrosisErythropoietin resistance

Serum P1,25D

Calcitriol

Renal Failure

PTH

Systemic ToxicityCVD

HypertensionInflammationCalcification

Immunological

25D

Ca++

Decreased Vitamin D Receptors and Ca-Sensing Receptors


Bone Loss Correlates With Severity of SHPT in CKD Stages 3 and 4

*P<0.05 compared with patients with PTH in the normal range.Z-Score = comparison to the mean value for women at a similar risk, including age, weight, and ethnicity.Rix et al. Kidney Int. 1999;56:1084-1093.

*

**


Bone-Fracture Rate Increases as CKD Progresses: Fractures in Patients on Dialysis

*Ratio of observed incidence of hip fracture in patients with kidney failure to expected incidenceof hip fracture in the general population.Adapted from Alem et al. Kidney Int. 2000;58:396-399.

0

5

10

100

<45 45-54 55-64 65-74 75-84 TotalAge (y)

Ob

serv

ed/E

xpec

ted

In

cid

ence

of

Hip

Fra

ctu

re*

Male Relative Risk = 4.4Female Relative Risk = 4.4

Overall

15

20

80

100 8799

25 20

10 10

7.56.4

2.4 2.54.4 4.4


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Cardiovascular Outcomes Worsen With CKD Progression: 3-Y Follow-Up by eGFR Levels

CHF = congestive heart failure.Anavekar et al. N Engl J Med. 2004;351:1285-1295.

Est

imat

ed E

ven

t R

ate

(%)

7560-7445-59<45P<0.001

eGFR (mL/min/1.73 m2)


Early treatment can make a difference

100

10

0

No Treatment

Current Treatment

Early Treatment

4 7 9 11

Time (years)

Kidney Failure

GFR

(m

L/m

in/1

.732

)

What can primary care providers do?

• Recognize and test at-risk patients

• Educate patients about CKD and treatment

• Focus on good glycemic control in people with diabetes

• For those with CKD:– Blood pressure below 130/80

– Use an ACE inhibitor or ARB

– More than one drug is usually required

– A diuretic should be part of the regimen

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What can primary care providers do?(Continued)

• Monitor eGFR and UACR

• Treat cardiovascular risk, especially with smokers and hypercholesterolemia

• Screen for anemia (Hgb), malnutrition (albumin), metabolic bone disease (Ca, Phos, PTH)

• Refer to dietitian for nutritional guidance

• Consult or team with a nephrologist

• Encourage labs to report estimated eGFR and urine albumin/creatinine ratios

Nephrology referral suggestions

• To assist with diagnostic challenge (e.g. decision to biopsy)

• To assist with therapeutic challenge (e.g. blood pressure)

• Rapid decay of estimated GFR

• Most primary kidney diseases, (e.g. glomerulonephridites)

• Preparation for renal replacement therapy, especially when GFR less than 30

Nephrology referral suggestions, cont.

• Regardless of when you refer:

• Obtaining preliminary evaluation (e.g. ultrasound, screening serologies)

• Providing consultant with patient history including serial measures of renal function

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Primary care providers –First line of defense against CKD

• Primary care professionals can play a significant role in early diagnosis, treatment, and patient education

• Therapeutic interventions for diabetic CKD are similar to those required for optimal diabetes care

• Control of glucose, blood pressure, and lipids

• A greater emphasis on detecting CKD, and managing it prior to referral, can improve patient outcomes

CKD is Part of Primary Care

References

Anavekar NS, McMurray JJ, Velazquez EJ, Solomon SD, Kober L, Rouleau JL, White HD, Nordlander R, Maggioni A, Dickstein K, Zelenkofske S, Leimberger JD, Califf RM, Pfeffer MA. Relation between renal dysfunction and cardiovascular outcomes after myocardial infarction. New England Journal of Medicine. 2004 Sep 23;351(13):1285-95.

Coresh J, Selvin E, Stevens LA, Manzi J, Kusek JW, Eggers P, Van Lente F, Levey AS. Prevalence of chronic kidney disease in the United States. Journal of the American Medical Association. 2007 Nov 7;298(17):2038-47.

Giatras I, Lau J, Levey AS. Effect of angiotensin-converting enzyme inhibitors on the progression of nondiabetic renal disease: a meta-analysis of randomized trials. Angiotensin-Converting-Enzyme Inhibition and Progressive Renal Disease Study Group. Annals of Internal Medicine. 1997 Sep 1;127(5):337-45.

Go AS, Chertow GM, Fan D, McCulloch CE, Chi-Yuan H. Chronic Kidney Disease and the Risks of Death, Cardiovascular Events, and Hospitalization. New England Journal of Medicine. 2004 Sep 23;351(13):1296-1305.

Hogg RJ, Furth S, Lemley KV, Portman R, Schwartz GJ, Coresh J, Balk E, Lau J, Levin A, Kausz AT, Eknoyan G, Levey AS; National Kidney Foundation's Kidney Disease Outcomes Quality Initiative. National Kidney Foundation's Kidney Disease Outcomes Quality Initiative clinical practice guidelines for chronic kidney disease in children and adolescents: evaluation, classification, and stratification. Pediatrics. 2003 Jun;111(6 Pt 1):1416-21.

References

Ix JH, Shlipak MG, Liu HH, Schiller NB, Whooley MA. Association between renal insufficiency and inducible ischemia in patients with coronary artery disease: the heart and soul study. Journal of the American Society of Nephrology. 2003 Dec;14(12):3233-8.

Jafar TH, Schmid CH, Landa M, Giatras I, Toto R, Remuzzi G, Maschio G, Brenner BM, Kamper A, Zucchelli P, Becker G, Himmelmann A, Bannister K, Landais P, Shahinfar S, de Jong PE, de Zeeuw D, Lau J, Levey AS. Angiotensin-converting enzyme inhibitors and progression of nondiabetic renal disease. A meta-analysis of patient-level data. Annals of Internal Medicine. 2001 Jul 17;135(2):73-87. Erratum in: Ann Intern Med 2002 Aug 20;137(4):299.

Levey AS, Greene T, Sarnak MJ, Wang X, Beck GJ, Kusek JW, Collins AJ, Kopple JD. Effect of dietary protein restriction on the progression of kidney disease: long-term follow-up of the Modification of Diet in Renal Disease (MDRD) Study. American Journal of Kidney Diseases. 2006 Dec;48(6):879-88.

National Diabetes Information Clearinghouse. Diabetes Control and Complications Trial (DCCT). Bethesda (MD): National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, US Department of Health and Human Services; 1993 (NIH Publication No. 02-3874). Available from: http://diabetes.niddk.nih.gov/dm/pubs/control/.

National Kidney Disease Education Program. Manuscript submitted for review. 2008.

National Kidney Foundation. K/DOQI clinical practice guidelines for chronic kidney disease: evaluation, classification, and stratification. American Journal of Kidney Diseases. 2002 Feb;39(2 Suppl 1):S1-266.

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References

O'Hare AM, Bertenthal D, Covinsky KE, Landefeld CS, Sen S, Mehta K, Steinman MA, Borzecki A, Walter LC. Mortality risk stratification in chronic kidney disease: one size for all ages? Journal of the American Society of Nephrology. 2006 Mar;17(3):846-53.

Sarnak MJ, Greene T, Wang X, Beck G, Kusek JW, Collins AJ, Levey AS. The effect of a lower target blood pressure on the progression of kidney disease: long-term follow-up of the modification of diet in renal disease study. Annals of Internal Medicine. 2005 Mar 1;142(5):342-51.

Shlipak MG, Smith GL, Rathore SS, Massie BM, Krumholz HM. Renal function, digoxin therapy, and heart failure outcomes: evidence from the digoxin intervention group trial. Journal of the American Society of Nephrology. 2004 Aug;15(8):2195-203.

Stevens LA, Fares G, Fleming J, Martin D, Murthy K, Qiu J, Stark PC, Uhlig K, Van Lente F, Levey AS. Low rates of testing and diagnostic codes usage in a commercial clinical laboratory: evidence for lack of physician awareness of chronic kidney disease. Journal of the American Society of Nephrology. 2005 Aug;16(8):2439-48.

U.S. Renal Data System, USRDS 2006 Annual Data Report: Atlas of End-Stage Renal Disease in the United States, National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD, 2006.

U.S. Renal Data System, USRDS 2007 Annual Data Report: Atlas of End-Stage Renal Disease in the United States, National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD, 2007.

current state of management in primary care. jayant kumar, md · - jafar, et al., 2001 • blood...

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