Creatine levels difficult to interpret
example:
At What Level of Creatinine Does a 65-Year-Old Diabetic, Hypertensive White Woman Weighing 50 Kilograms Have CKD?
• 77% said:
Creatinine > 1.5 mg / dl
– GFR = 37 mL/min/ 1.73 m2
– Ccreat = 30 mL/min
BUT
• Creatinine = 1.0 for GFR = 59 mL/min/1.73 m2
The Risk of Kidney Failure is Not Uniform
Relative risks compared to Whites:
African Americans 3.8 X
Native Americans 2.0 X
Asians/Pacific Islander 1.3 X
The relative risk of Hispanics compared to non-Hispanics is about 1.5 X
Risk factors for CKD
Nonmodifiable risk factor
- Older age
- Black Race
- Genotype
- Prematurity
Modifiable risk factor
- Hypertension
- Proteinuria
- Dyslipidemia
- Hyperuricemia
- Smoking
Mechanisms of Kidney Disease Progression
• Adaptive changes lead to maladaptive consequences
• Hypertension
• Hyperfiltration
– Elevated glomerular pressure
• Glomerular growth
– Increased wall stress
• Increased ammoniagenesis
• Complement activation and tubulo-interstitial disease
There are ~12 million adults in the US with CKD 3 or greater, but only ~500,000-600,000 patients with ESRD or a kidney transplant.
Why the disparity????
• Far more CKD patients die due to CVD than reach ESRD
• CKD is considered by some to be a coronary equivalent
– Data indicate that patients with lower GFRs (<45ml/min) and microalbuminuria or proteinuria carry a very high CVD risk (~ equivalent to a prior history of coronary disease).
Risk Factors for CVD in CKD
• Age
• Diabetes mellitus
• Smoking
• Hypertension
• Dyslipidemia
• Physical inactivity
• Menopause
• Obesity
• Anemia
• Hyperparathyroidism
• Hyperphosphatemia*
• Hypocalcemia
• Effects of dialysis
• Hypoalbuminemia and malnutrition
• Systemic inflammation
• Hyperhomocysteinemia
• Volume overload
UREMIA = urine in the blood
Uremia as a Clinical Syndrome
• Renal excretory failure
• Retained products of metabolism
• Related to protein intake
• Partially dialyzable
• Exact nature is unknown
• E.g. Small molecules (Urea etc.), lipid soluble molecules, middle molecules – urea (BUN), hormones, polyamines, middle molecules, serum proteases, trace elements, pyridine derivatives, 2-microglobulin
• Loss of metabolic and endocrine functions normally performed by the intact kidney
Uremia: Common Symptoms
• GI Nausea, vomiting, diarrhea
• CVS Dyspnea, edema, chest pain
• Neuro Restless legs, twitching, confusion
• Skin Pruritus, bruising, uremic frost
• MSK Bone pain, arthritis
Uremia: The Common Signs
• Sallow pallor, bruising
• Uremic fetor
• Hypertension
• Pericardial rub
• Alteration of consciousness
• Neuropathy
Alonzo Morning _NBA star FSGS
Adaptation of kidney function
Mechanisms of Adaptive Natriuresis in CKD
• Signal: ECF volume expansion
• Potential effectors
– Atrial natriuretic peptide (ANP)
– Other circulating natriuretic factors
– Local renal vasoactive factors
Clinical Manifestation of Sodium Balance in CKD
• Common ("Hoagie Night")
– Weight gain
– Peripheral edema
– Pulmonary edema
• Uncommon
– Renal Na wasting (ECF volume depletion)
– Weight loss
– Systemic hypotension
Potassium Homeostasis
Renal K Handling in CKD
- • K balance is very well maintained with progressive nephron loss
- • Filtered load of K decreases as GFR falls
- • K reabsorption is similar in normal and diseased kidneys
- • Adaptation: Distal K secretion is increased in proportion to the decrement in GFR
- via aldosterone
Mechanisms of Adaptive K Secretion in CKD
• Enhanced Na,K-ATPase activity
– Extracellular K concentration
– Aldosterone
• Increased distal tubular flow
– Adaptive natriuresis
– Osmotic diuresis per nephron
– Chronic metabolic acidosis
Hyperkalemia in CKD
• Aldosterone-related
– Hypoaldosteronism
• Idiopathic (Diabetes Mellitus)
• ACE inhibitors
– Pseudohypoaldosteronism
• K-sparing diuretics
• Distal flow-related
– ECF volume depletion
– Congestive heart failure (without diuretics)
• Insulin-related
– Diabetes mellitus
– Fasting
– Malnutrition
• Miscellaneous
– B-adrenergic agonists (esp. in diabetics)
– Dietary indiscretion
Anemia and Kidney Failure
Primary factors
- Relative erythropoietin deficiency
- Shortened rbc lifespan
- “uremic toxins”
- EPO may be a red blood cell “survival factor”
- Inhibitors of erythropoiesis--”uremic toxins”
Features of the anemia of CKD:
- Normocytic and normochromic
- Low reticulocyte count
- Normal bone marrow--and usually not needed to diagnose
- Serum erythropoieitin level low-normal--not needed to diagnose
Treatment of CKD Anemia
- Give EPO?
- but normalizing Hb leads to higher rate of death in CKD patients
- cut off is Hb or 7-8 g/dL
*Phosphate Homeostasis
coronary calcifications occur with high PO4 x Ca
Phosphate Homeostasis review articel
Bone/Ca/Phos/PTH Management
- • Low Phosphate diet
- • Maintain Ca X Phos product less than 55mg2/dl2
- • Phosphate binders with meals
- positive charge binders; e.g., calcium (Tums with meals)
- Use of Calcitriol or D3 analogues
- dampens stimulation of PTH
- • Monitor Ca, Phos, PTH
- • Avoid the use of aluminum
- neurotoxic
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