9. The CKD problem
• Clinically silent in the early stages
• Cost of renal disease can be extreme to
health care service
• Effects of renal disease can be extreme on
patient
• Treatments now available to slow progression
• Need an “early warning” system for CKD
10. Diseases of the Kidney
• Diabetes
• Hypertension
• Atherosclerosis
• Glomerular diseases
All global renal diseases
• Toxins
– Gentamicin
affect glomerular
– NSAIDS filtration rate (GFR)
– Compound analgesics
• Inherited diseases
• Tubular disorders
11. Definition of CKD
• Kidney damage for 3 months
– Defined by structural or functional abnormalities of
the kidney,
with or without decreased glomerular filtration rate
(GFR)
• Reduced GFR for 3 months
• New staging for chronic kidney disease (CKD)
is primarily based on kidney function.
National Kidney Foundation (NKF). Am J Kidney Dis. 2002;39(2 suppl 1):S1-S266.
12.
13. • Glomerular Filtration Rate is the volume of fluid passing
through the glomerulus in a given period of time.
• Influenced by renal perfusion pressure, renal vascular
resistance, glomerular damage, post-glomerular
resistance.
• “Normal Range” approx 90 - 150 mL/min
– Approx 170 L per day
• A larger healthy person has a higher GFR
– Can be reported as 90 - 150 mL/min/1.73m2
• Values fall with increasing age
14. Other reasons for estimating the GFR
• Monitoring progression of CKD
• GFR estimates are used for drug dosing
decisions
– Dosing of renally excreted drugs
– Avoiding nephrotoxic drugs
• Risk factor for cardiovascular disease
mortality
• Renal involvement in systemic diseases, such
as diabetes mellitus or SLE
28. Why are CKD/ESRD Patients
Predisposed to CV Disease?
CKD/ESRD
ANEMIA INFLAMMATION plus CaP deposition LVH/CHF
LIPIDS HTN
CAD and PVD
CV DISEASE AND DEATH
29. Why are CKD/ESRD Patients
Predisposed to CV Disease?
• 30-50% of ESRD patients have INFLAMMATION (increased
CRP, increased IL-6, decreased albumin)
– Increased CRP is a primary marker for inflammation predicting
cardiovascular disease in normal adults
– Increased CRP is the primary marker for increased cardiovascular
mortality on dialysis
• CKD/ESRD patients have metastatic calcification (coronary
arteries) because of secondary hyperparathyroidism and
elevated PO4 levels.
31. Distribution of hypertensives (65-89 years)
MEN WOMEN
ISOLATED
ISOLATED
SYSTOLIC
SYSTOLIC
59.3% 63.6%
30.3% 27.7%
10.4% 8.7%
COMBINED
COMBINED
ISOLATED ISOLATED
DIASTOLIC DIASTOLIC
Framingham study
32. Factors Affecting Blood Pressure
Blood Cardiac Total
Pressure = Output X Peripheral
Resistance
Amount of blood
ejected per minute Blood flow through
blood vessels
33.
34.
35. Prevalence of HTN in CKD
80% of patients with
glomerulonephritis
and 30% of patients
with chronic interstitial
disease are
hypertensive.
36.
37.
38. Aggressive BP Control, Proteinuria and
CKD Progression – what is the optimal BP
for CKD?
0
<1 gm/D 1-2.9 >3 gm/D
-2 gm/D
-4
Mean fall
<125/75
in GFR -6
(ml/min/yr) * <140/90
-8 *
-10
Klahr S et al, N Engl J
-12
Med 330:877, 1994
GOAL BP<125/75 if >1 gm proteinuria
39. Angiotensin II plays a central role in organ damage
Atherosclerosis* Stroke
Vasoconstriction
Vascular hypertrophy
Endothelial dysfunction Hypertension
A II LV hypertrophy
Fibrosis
Remodeling Heart Failure Death
Apoptosis MI
GFR
Proteinuria Renal Failure
Aldosterone release
Glomerular sclerosis
*Preclinical data.
LV = left ventricular; MI = myocardial infarction; GFR = glomerular filtration rate.