Carnitine content in different muscles of patients receiving maintenance hemodialysis.

OBJECTIVE: Chronic hemodialysis may lead to losses of carnitine from plasma and muscles. The aim of the present study was a comparison of carnitine contents in different human muscles (brachioradialis muscle and rectus muscle of abdomen) and evaluation of the correlation between plasma and tissue carnitine concentrations in patients receiving hemodialysis and healthy control patients. METHODS: The studies were performed in two groups of patients receiving hemodialysis. The first group included 37 patients (18 male, 19 female) (muscle specimen was taken from the brachioradialis muscle). The second group included 28 patients (15 male, 13 female) (muscle specimen was taken from the rectus muscle of abdomen). The other two separate groups of patients without renal involvement served as the controls. RESULTS: Significantly lower free plasma and free muscle carnitine (FMC) contents were noticed in patients receiving hemodialysis in comparison with the controls. Significantly higher total muscle carnitine (TMC) and FMC concentrations in the brachioradialis muscle in comparison with the rectus muscle of abdomen were observed in both the hemodialysis and control groups. Negative correlations between TMC, FMC, and FMC/TMC ratio versus duration of hemodialysis were found. No correlations between muscle and serum carnitine levels were observed. CONCLUSIONS: Patients receiving hemodialysis are carnitine deficient. Tissue carnitine depletion is related to hemodialysis duration. Carnitine concentration in blood does not represent the whole carnitine stores in patients receiving hemodialysis. Brachioradialis muscle carnitine contents are significantly higher than those in the rectus muscle of abdomen.

Randomized placebo-controlled study on the effects of losartan and carvedilol on albuminuria in renal transplant recipients.

BACKGROUND: The renoprotective effects of agents inhibiting the renin-angiotensin system in renal transplant recipients have been supposed but not finally proven. To shed more light on this issue, we performed a double-blind, placebo-controlled, crossover study to evaluate the influence of the AT-1 angiotensin II receptor blocker, losartan, on the surrogate marker of kidney injury, albuminuria, in patients after renal transplantation. The safety of this therapy was also evaluated. METHODS: Fourteen of 16 patients (nine male, five female), age 45.36 +/- 3.04 years, 65.5 +/- 10.0 months after kidney transplantation, with hypertension and stable serum creatinine 123 +/- 4 micromol/L without proteinuria, completed the protocol. Each patient underwent two 8-week treatment periods (one with losartan 50-100 mg and one with carvedilol 12.5-25 mg) in random order, allowing an 8-week placebo washout between treatments. The target office trough blood pressure was below 130/85 mmHg. RESULTS: The ambulatory blood pressure did not differ in the treatment periods. Losartan significantly reduced albuminuria relative to placebo and carvedilol (27.62+/-17.58 vs. 49.55 +/- 25.33 v. 44.77 +/- 21.9 mg/g creatinine; P < 0.01). A significant but not clinically relevant decrease in hemoglobin level after losartan was observed (losartan: 129 +/- 3.1 g/l, placebo: 134.2 +/- 3.2, carvedilol: 137.1 +/- 3.7; P < 0.001). Serum potassium, creatinine, creatinine clearance, and trough blood cyclosporine levels were unaffected. CONCLUSION: Losartan decreases microalbuminuria in renal transplant recipients with clinically minimal side effects.

Low-dose dual blockade of the renin-angiotensin system improves tubular status in non-diabetic proteinuric patients.

OBJECTIVE: Treatment with agents that inhibit the renin-angiotensin system is commonly regarded as a gold standard renoprotective strategy in patients with chronic kidney diseases. For maximum antiproteinuric effect, the dose titration of these agents is recommended. This therapeutic strategy is not used for proteinuric patients who are not able to receive high doses of angiotensin-converting enzyme inhibitor or angiotensin II receptor antagonists. MATERIAL AND METHODS: In patients with primary glomerulonephritis (n=24), a randomized, triple-treatment, triple-period, cross-over study was performed to compare the effects of combined therapy with benazepril 5 mg and losartan 25 mg and monotherapy with either agent alone at a two-fold higher dose on the extent of tubular injury as assessed by alpha1-microglobulin (alpha1-m) excretion and the plasma level of transforming growth factor-beta1 (TGF-beta1). RESULTS: Combination therapy significantly reduced alpha1-m excretion compared to either agent used alone: 178.29+/-27.36 to 99.63+/-13.03 mg/g creatinine for losartan + benazepril vs 178.29+/-27.36 to 161.59+/-23.22 mg/g creatinine for benazepril alone (p<0.05; ANOVA) and 178.29+/-27.36 to 99.63+/-13.03 mg/g creatinine for losartan + benazepril vs 178.29+/-27.36 to 173.45+/-27.69 mg/g creatinine for losartan alone (p<0.05; ANOVA). There was a significant correlation between change in alpha1-m excretion and reduction in proteinuria (r=0.704; p=0.023). There were no differences in TGF-beta1 level between the studied treatments. Systemic blood pressure reduction did not differ among the therapies. CONCLUSIONS: Combination therapy with angiotensin-converting enzyme inhibitor and angiotensin II subtype 1 receptor antagonists at very small doses may be superior to monotherapy with these agents at higher doses as far as tubular injury is concerned. We speculate that such a therapeutic strategy may be a useful approach for patients who are known not to be capable of receiving optimal renoprotective doses of these regimens.