It is well known that chronic inflammation has the potential to negatively impact nutritional status, risk of cardiovascular disease and, ultimately, mortality in adult hemodialysis (HD) patients.

Patients with inflammation have been shown to have lower albumin than those patients without inflammation. Therefore, these patients might benefit from interventions to ameliorate inflammation.

Inflammation can easily be identified using C-reactive protein (CRP) levels, but many dialysis centers do not regularly assess CRP. Thus, other means of assessing inflammation are needed. Both Axelsson et al. (Am J Clin Nutr. 2004;80:1222-1229) and Steiber et al. (J Ren Nutr. 2007;17:336-342) demonstrated the separation of malnourished versus inflamed patients using serum albumin and Subjective Global Assessment score. Table 1 shows the separation between malnourished with inflammation, pure malnutrition, and pure inflammation. According to this data set, 41% of the 19 patients had no nutritional loss, just pure inflammation.

Data supporting carnitine use

Once inflammation has been identified, what are the therapeutic options? To date, there have been very few clinical trials testing the effectiveness of interventions on ameliorating inflammatory status (J Intern Med. 2010; 268:456-467). Of the trials that have been done many are small and need replication.

Among these, is a new line of research highlighting the impact of carnitine on inflammatory markers such as CRP and interleukin-6. In three recent studies conducted by two independent groups, carnitine has been effective in decreasing CRP.

In the first study, 42 Turkish chronic HD patients were enrolled from a single dialysis center (Neph Dial Transplant. 2006;21:3211-3214). The patients were randomly assigned to either treatment with intravenous carnitine (20 mg/kg) while on dialysis treatment or no intervention. CRP decreased significantly in the treatment group, from a median 0.87 mg/dL at baseline to 0.17 mg/dL at six months. The investigators observed no significant decrease in the control arm. Concurrently, both the total protein and the serum albumin increased significantly. Of interest, the only inclusion criteria used for this study was receiving HD three times a week and no prior use of carnitine therapy.

Assessing the effects of dosing regimen

The second study was a randomized, double-blind clinical trial involving 26 Iranian chronic HD patients. Subjects were randomized to receive either 1,000 mg/day or oral carnitine or placebo for 12 weeks. The objective was to assess the effect of this dosing regimen of carnitine on anticoagulant factors and CRP. Patients had no inflammatory conditions and they had not received any anti-inflammatory agents prior to study enrollment (Ren Fail. 2010;32:1109-1114). Results showed carnitine had no effect on coagulation factors, but the drug did significantly decrease CRP in treatment arm (from 7.5 mg/dL at baseline to 4.4 mg/dL at 12 weeks. The researchers observed no significant change in CRP in the placebo arm.

Carnitine’s effect on inflammation

The third study, by the same Iranian team, up, however, was conducted to assess the effect of carnitine on inflammation, lipoprotein a (Lp(a)), and oxidative stress (Hemodial Int. 2010;14:498-504). The study was an unblinded, randomized clinical trial where the intervention group received 1,000 mg/day of oral carnitine and the placebo group received no supplement. At the conclusion of the 12-week intervention period, the treatment group had significant decreases of 29% in CRP and 61% in interleukin-6 while no significant changes occurred in the placebo group.  In addition, this study was unable to demonstrate a change in the oxidative stress parameter.

All three of these studies have small sample sizes and two were not double-blind. However, the CRP-related results were consistent. These findings are also substantiated in an older study by Savica et al (J Ren Nutr. 2005;15:225-230), who demonstrated significant decreases in CRP in a sample of 65 HD patients. While carnitine is an inexpensive therapy with little to no adverse effects, more work needs to be done to elucidate the mechanisms underlying carnitine’s effect on CRP.

In general, the presence of inflammation needs to be monitored regularly in the HD patient population and, if possible, clinicians should intervene to reduce the chronic inflammatory status in these patients.

Table 1. Subjective Global Assessment in Chronic Kidney Disease

Subjective Global Assessment Score

3

(moderate loss)

4

(moderate loss)

5

(moderate loss)

6

(mild loss)

7

(no loss)

Body Mass Index, (p<0.004)

23.6+2.2

21.2+3.9

27.6+7.9

28.9+7.5

28.7+6.1

Age (years), NS

56.5+12.0

69.3+13.4

63.4+14.7

65.6+13.3

61.4+13.9

Duration on Dialysis, NS

47.0+48.1

45.4+43.1

41.8+32.6

39.3+34.5

41.5+34.0

Serum Albumin (mg/dL), (p<0.001)

2.9+1.2

3.4+0.7

3.7+0.5

3.8+0.4

3.8+0.3

% with Albumin < 3.8

     Sample size (n)

     Mean+SD

67%$

2

2.3+0.5

56%$

5

2.9+0.5

63%$

20

3.4+0.3

39%$$$

25

3.5+0.2

41%$$$

19

3.5+0.2

% with Albumin > 3.8

     Sample size (n)

     Mean+SD

33%$$

1

4.2

44%$$

4

4.0+0.3

37%$$

12

4.1+0.2

61%

39

4.1+0.3

59%

27

4.0+0.2

*SGA = subjective global assessment category, NS = not significantly different
$ = serum albumin < 3.8 + SGA (3-5) = malnutrition with inflammation
$$ = serum albumin >3.8 + SGA (3-5) = pure malnutrition
$$$ = serum albumin <3.8 + SGA (6-7) = pure inflammation
Source: J Ren Nutr. 2007;17:336-342.

Dr. Steiber is Coordinator of the Dietetic Internship/Master’s Degree Program at Case Western Reserve University in Cleveland.