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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.

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New concepts in chronic kidney disease

New Concepts in Chronic Kidney Disease

Jonathan B. Jaffery, MD

Assistant Professor of Medicine

University of Wisconsin-Madison


New concepts in chronic kidney disease1
New Concepts in Chronic Kidney Disease

  • The Epidemic

  • Estimating GFR & Staging

  • Risk factors for progression

  • Role of Angiotensin II

  • Management




Patient awareness of ckd
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


Estimating GFR

  • 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)

(140-Age)(Weight)

Ccr(ml/min)=

(0.85 if female)

72(Scr)

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
CKD Staging

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



Chronic kidney disease progression risks
Chronic Kidney Diseaseprogression risks

  • Hypertension

  • Proteinuria

  • Glycemic control

  • Smoking

  • Lipids




Measuring proteinuria
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
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
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
CKD Progression Risks lipids

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


Ace inhibitors and ckd progression meta analysis
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


ACEi/ARB

100

GFR

80

60

40

20

0

Time


Acei arb and gfr
ACEi/ARB and GFR

60

100

Heart Rate

50

80

40

GFR

60

30

40

20

20

10

0

0

b-Blocker

ACEi/ARB


Chronic kidney disease management

Slow the progression

• Blood pressure • Smoking

• Proteinuria• Lipids

• Protein restriction • Glycemic control

Evaluate and treat complications

• Anemia • Osteodystrophy

Prepare for renal replacement therapy

• Vascular access • Referral to Nephrology

Chronic Kidney Disease management


Chronic kidney disease management1
Chronic Kidney Disease management

  • 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



I slowing the progression of ckd proteinuria
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?


I slowing the progression of ckd protein restriction
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
Protein Restriction (0.6 gm/kg) and DM Nephropathy

Zeller K et al, N Engl

J Med 324:78, 1991

Walker JD et al, Lancet 2:1411, 1989


Ii managing complications of ckd anemia
II. Managing complications of CKDAnemia

  • 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


II. Managing complications of CKDOsteodystrophy

  • 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 CKDOsteodystrophy

  • Dietary phosphate restriction

  • Phosphate binders

    • Calcium carbonate, Calcium Acetate

    • Lanthanum Carbonate

    • Sevalamer

  • 1,25 Vitamin D

  • Calcimimetic- not approved for pre-ESRD


Iii preparing for rrt vascular access
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
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
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


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