Chronic Kidney Disease
Chronic Kidney Disease
Chronic Kidney Disease
Definition
Chronic, irreversible loss of kidney function attributable
to loss of functional nephron mass pathophysiologic
processes for more than 3 months.
Pathophysiology of CKD
Final Common Pathway is loss of nephron mass
Diabetes
Hypertension Mediated by vasoactive
Loss of Structural/ Functional
Chronic GN molecules, cytokines and
Nephron Mass Hypertrophy of remnant nephrons growth factors, renin
Cystic Disease
Tubulointerstitial disease angiotensin axis
Sclerosis
of remnant
nephrons
Estimation of GFR
Stage 1 and 2
Asymptomatic, hypertension
Stage 3 and 4
Anemia loss of energy
Decreasing appetite; poor nutrition
Abnormalities in Calcium, Phosphorus metabolism
Sodium, water, potassium and acid base abnormalities
Stage 5
All of the above accentuated; eventually overt uremia
Estimates of Subgroups at
Increased Risk for CKD
Subgroup Estimated Numbers
2002-03
Common Causes and
Presentation
1.6
1.4
1.2
1/Cr Function
0.8
0.6
0.4
0.2
0
1998 1999 2000 2001 2002 2003 2004
Clinical Features of Diabetic CKD
Clinical Features of Non-Diabetic
CKD
Pathophysiology of Uremia
Potassium
GI excretion is augmented
Constipation, dietary intake, protein catabolism,
hemolysis, hemorrhage, transfusion of stored blood,
metabolic acidosis,
Drugs: ACE inhibitors, ARBs, B blockers, K sparing
diuretics and NSAIDs
Hyporeninemic hypoaldosteronism: Diabetes, sickle
cell disease
Acid Base Imbalance
Damaged kidneys are unable to excrete the 1 mEq/kg/d
of acid generated by metabolism of dietary proteins.
NH3 production is limited because of loss of nephron mass
Decreased filtration of titrable acids sulfates, phosphates
Decreased proximal tubular bicarb reabsorption, decreased
positive H ion secretion
Arterial pH: 7.33 - 7.37; serum HCO3 rarely below 15
buffering offered by bone calcium carbonate and
phosphate
Should be maintained over 21
Treatment: Sodium bicarbonate, calcium carbonate,
sodium citrate
Bone Disease
Treatment of Secondary
Hyperparathyroidism
Phosphorus control in diet
Phosphate binders
Calcium acetate (Phoslo), calcium carbonate (TUMS),
sevelamer (Renagel) , lanthanum (Fosrenol)
Oral Vitamin D
Calcimemetic agent: Cinacalcet (Sensipar)
Mineral Metabolism
Calciphylaxis
Calcemic uremic arteriopathy
Extraosseous/metastatic
calcification of soft tissues and
blood vessels
Devastating complication
Treatment: controversial
Sodium thiosulfate
Parathyroidectomy
Cardiovascular Abnormalities
Leading cause of
morbidity and mortality in
patients with CKD at all
stages
Ischemic CAD
Hypertension and LVH
Congestive heart failure
Uremic pericarditis
Trends in the interactions of diabetes,
congestive heart failure, & CKD: 2002-
2003
LVH and dilated CM are
the most ominous risk
factors for excess mortality
and morbidity
High cardiac output
Extracellular fluid overloa
AV shunt
Anemia
Non Pharmacologic
Risk Factor Modification
Pharmacologic
Treatment of complications
Therapeutics in CKD
Non Pharmacologic
Risk Factor Modification
Pharmacologic
Treatment of complications
Therapeutics in CKD
Non Pharmacologic
Risk Factor Modification
Pharmacologic
Treatment of complications