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
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
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 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.
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
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
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
• 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
• 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