Perit Dial Int
27(Supplement_2):
235-238
2007
© 2007 International Society for Peritoneal Dialysis
ASSOCIATION OF CARNITINE DEFICIENCY IN INDIAN CONTINUOUS AMBULATORY PERITONEAL DIALYSIS PATIENTS WITH ANEMIA, ERYTHROPOIETIN USE, RESIDUAL RENAL FUNCTION, AND DIABETES MELLITUS
S. Ramalakshmi1,
Bjoe Baben1,
Ben S. Ashok1,
V. Jayanthi2,
Nancy Leslie2 and
Georgi Abraham1
Department of Nephrology,1 SRMC & RI, and
Madras Medical Mission,2 Chennai, India
Correspondence to: G. Abraham, Department of Nephrology, SRMC&RI, Porur,
Tamil Nadu, India.
abraham_georgi{at}yahoo.com
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ABSTRACT
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Objective: In the present study, we aimed to determine
levels of free carnitine in hemodialysis (HD) and peritoneal dialysis (PD)
patients in India and to correlate carnitine deficiency with various clinical
parameters.
Methods: Patients on HD and PD at two tertiary care
centers were selected for the study. Baseline data were obtained, and a free
carnitine analysis was performed. Carnitine deficiency was defined as a free
carnitine level of less than 40 µmol/L.
Results: The total number of study patients was 96 (77
on HD, 19 on PD). In the PD group, the mean age was 56 years, with 26.3% of
the patients being vegan, 47.4% having diabetes, and 57.9% having a daily
urine output of <500 mL. The mean carnitine level in that group was 38.9
µmol/L, and 68.4% of the patients had a carnitine deficiency. A Pearson
correlation test failed to show any association of carnitine level with
parameters such as anemia, use of erythropoietin, non-vegetarian diet,
diabetes, and hypertension. In the HD group, the mean age was 45 years, with
22% of the patients being vegan, 23% having diabetes, and 45.5% having a daily
urine output of <500 mL. The mean carnitine level in the group was 38.2
µmol/L, and 64.3% of the patients had a carnitine deficiency. Residual
renal function and duration of dialysis were different in HD patients with and
without carnitine deficiency. Carnitine levels in the HD group correlated
positively and statistically significantly with the presence of diabetes and
hypertension.
Conclusion: This study is the first demonstration that
Indian dialysis patients have carnitine deficiency.
KEY WORDS: Carnitine deficiency; CAPD; hemodialysis; anemia; residual renal function.
Carnitine is a water-soluble molecule that is present in almost all animal
species. It is an important intermediary in fat metabolism. Patients on
dialysis and those with chronic renal failure appear to have abnormal renal
handling of carnitine, leading to symptoms of lethargy, muscular weakness,
cardiac dysfunction, and recurrent cramps. This symptom constellation has been
termed "dialysis-related carnitine deficiency" and occurs because
of the disparity between carnitine availability and metabolic need. The aim of
the present study was to demonstrate carnitine levels in hemodialysis (HD) and
peritoneal dialysis (PD) patients, and to correlate carnitine deficiency with
various clinical parameters.
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PATIENTS AND METHODS
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Study patients with stage V chronic kidney disease on maintenance dialysis
(HD and PD) were selected from two tertiary care centers. Baseline
characteristics such as age, dialysis duration, type of diet, underlying renal
disease, residual renal function (RRF), serum total protein, serum albumin,
hemoglobin, and use of erythropoietin (EPO) were collected.
BIOCHEMICAL ANALYSIS
We collected 3 mL fasting whole blood samples in standard sample tubes
treated with ethylenediaminetetraacetic acid. In patients on HD, blood was
collected before a HD session. Samples were centrifuged at 3000g for
10 minutes, and the plasma was separated. The plasma was then deproteinized by
centrifugation for 20–40 minutes with Amicon Centricon filters
(Millipore, Billerica, MA, U.S.A.) having a molecular weight cut-off of
2000–5000.
A commercial kit and the modified method of Marquis and Fritz
(1) was then used to analyze
the resulting filtrate for level of free carnitine. Spectrometric enzyme
analysis was performed on a random-access, fully-automated chemical analyzer.
Carnitine deficiency was defined as a free carnitine level of less than 40
µmol/L.
STATISTICAL ANALYSIS
Descriptive statistics (mean and standard deviation) are used to present
patient data. Comparisons between patient groups (with and without carnitine
deficiency) used the t-test analysis. The Pearson correlation
coefficient and the chi-square test were used to look for associations between
carnitine level and various independent variables.
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RESULTS
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The total number of study patients was 96 (77 on HD, 19 on PD).
Table 1 describes the PD and HD
groups.
In the PD group, the mean carnitine level was 38.87 ± 13.66
µmol/L (range: 21–70 µmol/L), and in the HD group, it was 38.25
± 11.91 µmol/L (range: 19.6–82 µmol/L,
Table 2). In the PD and HD
groups respectively, 68.42% and 64.93% of patients were carnitine-deficient
(Table 3).
In the PD group, a comparison of the patients with and without carnitine
deficiency revealed no differences in age, hemoglobin, total protein, serum
albumin, RRF, or dialysis duration. We then tested correlations between serum
carnitine level and other clinical parameters. No statistically significant
associations were observed in the PD group with regard to the various
parameters tested (Table
4).
In the HD group, patients with and without carnitine deficiency showed a
statistically significant difference in RRF (<500 mL daily, p =
0.000) and in dialysis duration (p = 0.007). In addition, carnitine
levels in this group correlated positively with the presence of diabetes and
hypertension. No associations with the other tested parameters (diet, anemia,
EPO use) were observed (Table
5).
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DISCUSSION
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Treatment of carnitine deficiency in the dialysis population is gaining in
popularity because the condition is easily recognized and
L-carnitine supplements are easily available. Carnitine
supplementation may also be useful in treating severe symptoms that might
otherwise be labeled uremic.
Carnitine is crucial for energy production in cardiac and skeletal muscles.
It plays an indispensable role in the metabolism of fatty acids, where it is
involved in the transport of activated fatty acids between various cellular
compartments (2). Reactions of
carnitine with activated fatty acids are catalyzed by carnitine
acyltransferases:
Carnitine is derived from red meat and dairy products and biosynthesized in
liver, kidney, and brain. Free carnitine is filtered at the glomerulus, with
more than 90% undergoing tubular reabsorption. In the dialysis population,
free carnitine is lower and acylcarnitine is higher than in the general
population. This shift may be attributable to loss of renal parenchyma, poor
clearances, and poor dietary intake
(3). Carnitine deficiency leads
to multiple comorbidities such as poor exercise tolerance, anemia, and cardiac
dysfunction.
The present study is the first in India that assesses free carnitine levels
in the Indian dialysis population. In our PD and HD groups alike, more than
half of the patients showed carnitine deficiency. Average carnitine values
were similar in both groups.
In the HD group, RRF was significantly different in the patients with and
without carnitine deficiency. That finding emphasizes the vital role that the
kidneys play in maintaining carnitine balance. No association of carnitine
level with RRF was found in the PD group, a result that could be a result of
the small sample size.
Although carnitine comes mainly from animal fats, we found no correlation
between carnitine and a vegan or non-vegan diet. However, even the South
Indian nonvegetarian diet contains little in the way of meat products, such
products usually being consumed only once or twice weekly—which may
explain the lack of an association.
Available data indicate that the free carnitine levels are typically normal
in PD patients, but our data show carnitine deficiency in these patients. The
reduction in plasma L-carnitine levels occurred within the first
few months of dialysis, and muscle levels continued to decline even after 1
year (4); however, our study
found no association between carnitine level and dialysis duration.
Serum albumin is a marker of nutrition status, and serum albumin levels in
our patients were not significantly associated with carnitine levels.
Supplementary L-carnitine has been used as an adjunct treatment in
dialysis patients with EPO-resistant anemia, but its possible mechanism of
action is unknown. Carnitine has been shown to increase the erythroid
colony–forming units in mouse bone marrow
(5). We found no association
between anemia, EPO use, and free carnitine levels in the present study.
Chronic conditions such as diabetes and heart failure also have been
reported to cause carnitine deficiency
(6). We found positive
correlations between carnitine deficiency and diabetes and hypertension in our
HD patients.
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CONCLUSIONS
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The present study demonstrates that HD and PD patients in the Indian
dialysis population can both have carnitine deficiency. The causes are likely
multifactorial and connected to dietary practices. We found an association
between serum carnitine level and RRF in HD patients, and all possible means
should be used to preserve RRF. Understanding carnitine deficiency and
treating it may improve quality of life in our dialysis patients.
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REFERENCES
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ABSTRACT
PATIENTS AND METHODS
