AJKD 2003 Supplement Issue - Salbi Flashcards
When was levocarnitine approved by the FDA for the prevention and treatment of carnitine deficiency in patients with end-stage renal disease who are undergoing dialysis?
In 1999. *bonus: Health Canada approved Levocarnitine Injection for use in ESRD patients on Hemodialysis in 2001 (Source: AJKD, Eknoyan, 2003)
What type of molecule is Carnitine?
A soluble low-molecular-weight compound. (Source: AJKD/Hoppel/2003)
How is Carnitine made available to the body?
From diet and also biosynthesized from the essential amino acids lysine and methionine. (Source: AJKD/Hoppel/2003)
In a healthy person, where is most of the amount of Carnitine found?
Typically, approximately 80% to 85% of carnitine exists as the free form in plasma. (Source: AJKD/Hoppel/2003)
What would indicate physiological abnormalities caused by inadequate carnitine?
Decreased absolute content of free carnitine or a greater than normal ratio of acylated carnitine to free carnitine (>0.4). (Source: AJKD/Hoppel/2003)
What are the normal plasma levels of Carnitine in a healthy adult?
Approximately 40 to 50 mol/L in healthy adult men. (Source: AJKD/Hoppel/2003)
What are the main dietary sources?
Animal products, particularly red meat and dairy. (Source: AJKD/Hoppel/2003)
How and where is Carnitine biosynthesized?
From the essential amino acids lysine and methionine; in the liver and kidneys.(Source: AJKD/Hoppel/2003)
What is the protective role of Carnitine related to Acyl CoAs
Carnitine is believed to have a protective role by removing long-chain acyl CoAs from cell membranes, thereby stabilizing them.(Source: AJKD/Hoppel/2003)
How much Carnitine is lost during a hemodialysis session?
As much as a 75% reduction in plasma free carnitine concentration, but by 8 hours after dialysis, concentrations have returned to predialysis values.(Source: AJKD/Hoppel/2003)
What are the benefits of Carnitine therapy to treat patients with heart failure?
Typical benefits include improved exercise capacity and peak oxygen consumption, reduced fatigue, and improved muscle conditioning. The role of carnitine in patients with ischemic heart disease is controversial; nonetheless, carnitine has been shown to protect the myocardium in these patients.(Source: AJKD/Hoppel/2003)
What has been shown in chronic hemodialysis patients and carnitine supplementation?
Improve myocardial fatty acid metabolism, cardiac arrhythmias, and other aspects of impaired cardiac function typically related to impaired fatty acid metabolism. Skeletal muscle function has been an especially significant target for carnitine therapy; numerous studies have reported such improvements as reduced muscle cramps, improved exercise performance, increased muscle strength and mass, decreased asthenia and dyspnea, and increased peak oxygen consumption. (Source: AJKD/Hoppel/2003)
What is associated with patients with long-term intermittent hemodialysis (ie, two to three sessions weekly for > 6 months) ?
A reduction in plasma and tissue L-carnitine levels, as well as disturbances in carnitine homeostasis and relative levels of the various carnitine esters. (Source: AJKD/Evans/2003)
Why are high tissue to plasma concentration ratios maintained?
For skeletal and cardiac muscle, which both have a critical reliance on fatty acid oxidation as an energy source, but are incapable of synthesizing L-carnitine. (Source: AJKD/Evans/2003)
What are the normal plasma ranges in healthy adult men and women?
L-carnitine: 40 - 50 umol/L; Acetyl-L-carnitine: 3 - 6 umol/L Note: *Plasma or serum L-carnitine levels tend to be approximately 10% to 20% lower in women. (Source: AJKD/Evans/2003)
How much carnitine is synthesized in a healthy adult?
Approximately 1 to 2 mol of L-carnitine per kg of body weight per day, representing 10 to 20 mg/d for an average adult. (Source: AJKD/Evans/2003)
Where does the body house its greatest pool of carnitine?
In the skeletal muscle (98%), with most of the remaining 2% residing in such organs as the liver, kidney, and heart. (Source: AJKD/Evans/2003)
Describe the findings from the Australian group (Fig. 3): plasma levels of L-carnitine in a group of 21 patients with ESRD during their first 12 months of hemodialysis therapy.
Mean (SE) predialysis plasma concentrations of L -carnitine during the first 12 months of hemodialysis in patients (n = 21) with ESRD. Within the first month of dialysis therapy, plasma L -carnitine levels had decreased to less than the normal level. Plasma levels continued to decline and showed no clear signs of becoming constant after 12 months. (Source: AJKD/Evans/2003)
In patients with kidney failure, what is the correlation between muscle L-carnitine level and dialysis age?
Negative correlation. The majority of patients who have been on hemodialysis therapy for more than 12 months will have plasma L-carnitine levels less than the normal range. (Source: AJKD/Evans/2003)
What dose should be given at the end of a dialysis and why is in IV form?
IV dose of 20 mg/kg at the end of dialysis will lead to typical plasma concentrations of 1,000 umol/mL. These “supraphysiological” plasma L -carnitine levels are required to drive the compound from plasma into skeletal muscle cells. Whereas intravenously administered Lcarnitine is fully bioavailable and negligibly metabolized (except through incorporation into the endogenous carnitine pool), orally administered L-carnitine is poorly absorbed and possibly acetylated during the absorption process (Source: AJKD/Evans/2003).
What have been some of the findings related to cardiology patients supplemented with carnitine?
- statistically significant improvement in exercise duration 2. improved long-term patient survival (Kaplan-Meier) 3. significant reduction in LV dilatation, which is a powerful predictor of reduced mortality. (Source: AJKD/Pauly/2003)
How does carnitine affect patients with ischemic cardiomyopathy?
Carnitine treatment in combination with other traditional pharmacological therapy might have an additive effect for the improvement of LV function in ischemic cardiomyopathy (Gurlek et al). (Source: AJKD/Pauly/2003)
What is the relationship between hypotension and HD patient?
The relationship between hypotension and elevated mortality was shown in a national random sample of 4,499 hemodialysis patients. A low predialysis systolic BP was associated with an elevated relative risk for mortality. This relationship was observed in patients with and without diabetes and patients with and without heart failure. (Source: AJKD/Pauly/2003)
What are the effects of carnitine therapy in patients without kidney disease and those with kidney disease?
Without kidney disease: positive effects on measures and outcomes of MI, heart failure, and angina. (Source: AJKD/Pauly/2003)