Chronic Kidney Disease

 Chronic Kidney Disease

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

MDRD Calculator online

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

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2735026/

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