New Concepts in Chronic Kidney Disease

Jonathan B. Jaffery, MD

Assistant Professor of Medicine

University of Wisconsin-Madison

New Concepts in Chronic Kidney Disease

• The Epidemic

• Estimating GFR & Staging

• Risk factors for progression

• Role of Angiotensin II

• Management

USRDS, 2000

Incidence/Prevalence of ESRD in the US

Trivedi et al, AJKD 39: 721-9, 2002

Patient awareness of CKD

Proportion of individuals who were ever told that they had weak or failing kidneys by the level of GFR (ml/min per 1.73 m2), elevated urinary albumin to creatinine ratio (ACR; mg/g) and gender.

Coresh et al, JASN 16: 180-188, 2005

• Cockcroft-Gault Equation1

• MDRD Equation2

GFR(ml/min/1.73m2)=

170 (Scr)-0.999(Age)-0.176(SUN)-0.170(Alb)+0.318

(0.762 if female)(1.180 if black)

72(Scr)(0.85 if female)

(140-Age)(Weight)Ccr(ml/min)=

1 Cockcroft and Gault, Nephron 1976 2 Levey et al, Ann Intern Med 1999

Estimating GFR

Estimating GFR

• Modified MDRD equation– e-GFR = 186 x (PCR)-1.154 x (Age)-0.203 x (0.742 if

female) x (1.210 if African American)

• Convince the lab to do it automatically• On-line e-GFR calculators

– http://www.nkdep.nih.gov/healthprofessionals/tools/gfr_adults.htm

– http://www.kidney.org/kls/professionals/gfr_calculator.cfm

CKD Staging

K/DOQI guidelines, AJKD, Vol. 39, No 2, Suppl 1, February 2002

Sample e-GFR

Serum Creatinine

Age Male Female

1.2 mg/dl

35 73 54

70 64 47

2.0 mg/dl

35 41 30

70 35 26

Chronic Kidney Diseaseprogression risks

• Hypertension

• Proteinuria

• Glycemic control

• Smoking

• Lipids

CKD Progression Riskshypertension

CKD Progression Risks proteinuria

U protein on Ccr

-20

-18

-16

-14

-12

-10

-8

-6

-4

-2

0

-2 0 2 4 6 8 10

U protein; g/d

Slo

pe m

l/m

in/y

All MAP

Norm BP

Hi BP

Measuring proteinuria

• The ratio of protein or albumin to creatinine in an untimed (spot) urine sample is an accurate alternative to measurement of protein excretion in a 24-hour urine collection.

CKD Progression Risks glycemic control

Cumulative Incidence of Urinary Albumin Excretion {300 mg per 24 Hours (Dashed Line) and 40 mg per 24 Hours (Solid Line)} in Patients with IDDM Receiving Intensive or Conventional Therapy.

Diabetes Control and Complications Trial Research Group, N Engl J Med 329:977, 1993

CKD Progression Risks smoking

Mean calculated glomerular filtration rate (GFR) at each year after study entry during the 5-year follow-up in smokers (—•—) versus nonsmokers (—     —) with established diabetic nephropathy.

*P < 0.03 versus nonsmokers.

CKD Progression Risks lipids

Samuelsson O et al, Nephrol Dial Transplant. 1997 Sep;12(9):1908-15

ACE Inhibitors and CKD ProgressionMeta-analysis

• 11 randomized controlled trials comparing ACE inhibitors vs. other medications in treatment of hypertension in 1860 nondiabetic patients with CKD (S Cr=2.3).

• Results: – ACE inhibitors lowered BP and proteinuria.– ACE inhibitors decreased the combined risk of

progression of CKD and development of ESRD by 30%, independent of BP lowering effects.

Jafar T, Ann Intern Med 135:73-87, 2001

http://www.hypertensiononline.org/slides2/slide01.cfm?q=ramipril+efficacy+in+nephropathy+study&pg=1

GF

R

100

80

60

40

20

0

Time

ACEi/ARB

ACEi/ARB and GFR

100

80

60

40

20

0

Hea

rt R

ate

60

50

40

30

20

0

10

GF

R

-Blocker ACEi/ARB

Chronic Kidney Disease management

I. Slow the progression• Blood pressure • Smoking

• Proteinuria • Lipids

• Protein restriction • Glycemic control

II. Evaluate and treat complications• Anemia • Osteodystrophy

III. Prepare for renal replacement therapy• Vascular access • Referral to Nephrology

• National Kidney Foundation Kidney Disease Outcome Quality Initiative (K/DOQI)– The Kidney Disease Outcomes Quality Initiative or

K/DOQI provides evidence-based clinical practice guidelines developed by volunteer physicians and health care providers for all stages of chronic kidney disease and related complications, from diagnosis to monitoring and management.

– http://www.kidney.org/professionals/kdoqi/index.cfm

Chronic Kidney Disease management

I. Slowing the progression of CKD

Hypertension

I. Slowing the progression of CKD

Proteinuria• ACEi or ARB

• Nondihydropyridine calcium channel blockers (verapamil and diltiazem)– have been shown to effective in reducing

urinary albumin excretion, beyond ability to lower blood pressure (Bakris GL et al, Kidney Int. 2004 Jun;65(6): 1991-2002)

• Combinations?

http://www.hypertensiononline.org/slides2/slide01.cfm?q=calcium+channel+blocker&pg=1

I. Slowing the progression of CKD Protein Restriction

• Animal studies - dietary protein restriction significantly slows development of renal disease

• MDRD Study

• 585 nondiabetic patients with GFR 39 ml/min randomized to either 1.1 or 0.7 gm protein/kg/day

• Results – Reduction of protein intake minimally ameliorated decline of GFR (1.1 cc/min/year)

Protein Restriction (0.6 gm/kg) and DM Nephropathy

-1.2

-1

-0.8

-0.6

-0.4

-0.2

0

Walker Zeller

Ch

ange

GF

R (

mL

/min

/mon

th)

Control

Low

Walker JD et al, Lancet 2:1411, 1989

Zeller K et al, N Engl J Med 324:78, 1991

II. Managing complications of CKD

Anemia• Diagnosis of exclusion

• Check iron stores– TSAT (iron/TIBC) 20-50%– Ferritin 100-600 ng/ml

• Erythropoietin replacement therapy

• Goal Hg 11-12 g/dL

• High-turnover (osteitis fibrosa cystica) bone disease

• Low-turnover (adynamic) bone disease– Resistance to PTH– Need for relatively higher PTH levels to

maintain adequate bone remodeling– Low-turnover may have worse outcomes than

high

• Check phosphorous, calcium, intact PTH

II. Managing complications of CKD

Osteodystrophy

II. Managing complications of CKD

Osteodystrophy

• Dietary phosphate restriction

• Phosphate binders– Calcium carbonate, Calcium Acetate– Lanthanum Carbonate– Sevalamer

• 1,25 Vitamin D

• Calcimimetic- not approved for pre-ESRD

II. Managing complications of CKD

Osteodystrophy

III. Preparing for RRTVascular access

• Goal is to:– Increase use of fistulas– Avoid use of tunneled catheters

• Save the Veins!

• Avoid blood draws/IVs in non-dominant arm

• NO subclavian central lines

III. Preparing for RRT Referral

• > 50% of patients had 1st encounter with nephrologist within 1 year of RRT

• 32% had 1st appt < 4 months before ESRD

• Patients referred late (< 4 months before ESRD) had 72% greater mortality during the first year of HD compared with patients referred early (> 4 months before ESRD)

Stack AG, AJKD February 2003

Chronic Kidney Disease summary

• CKD- common final pathway• Stage using MDRD equation• Use spot urine protein:creatinine ratio• Goal is:

– Prevention– Slow progression of disease– Prevent and manage complications

• Control of proteinuria & blood pressure– RAAS inhibition

• Early referral to nephrology