Mari Odamaki

Association between inflammatory mediators and muscle mass in long-term hemodialysis patients

BACKGROUNDnMuscle wasting is highly prevalent in long-term hemodialysis (HD) patients. Although inflammatory indices have been associated with malnutrition in these patients, the role of inflammation in muscle wasting has not yet been determined.nnnMETHODSnThe relationship between the inflammatory mediators C-reactive protein (CRP) and interleukin-6 (IL-6) and the muscle mass indices thigh muscle area (TMA), measured by computed tomography, and creatinine (Cr) production, estimated by the Cr kinetic model (Cr-CKM), were investigated in 188 HD patients.nnnRESULTSnSerum IL-6 level (7.3 +/- 7.8 pg/mL) was significantly elevated in HD patients, whereas mean serum CRP level (4.8 +/- 7.5 mg/L) remained within the normal range. Similar to serum albumin, muscle mass indices had significantly negative correlations with both serum IL-6 and CRP levels (TMA/dry weight [DW] versus log IL-6, r = -0.28; P < 0.01; TMA/DW versus log CRP, r = -0.38; P < 0.001; Cr-CKM versus log IL-6, r = -0.31; P < 0.01; Cr-CKM versus log CRP, r = -0.24; P < 0.01). Although muscle mass indices also were associated with both age and sex, a multiple regression analysis confirmed that these inflammatory indices were significantly associated with muscle mass in HD patients.nnnCONCLUSIONnData indicate that muscle wasting is associated closely with inflammatory indices in long-term HD patients. It may be important to clarify the mechanism for the increasing inflammatory status and suppress the inflammatory response in these patients to improve their malnutrition and recover muscle mass.

Association between Plasma Adiponectin Concentration and Visceral Fat Accumulation in Hemodialysis Patients

Background: Cardiovascular diseases resulting from atherosclerotic complications are major causes of death in hemodialysis (HD) patients. Adiponectin (ADPN) is a recently discovered adipocyte-derived protein that appears to have protective role against atherosclerosis. HD patients have an excess accumulation of intra-abdominal fat mass in association with an atherogenic serum lipid profile despite low body mass index; however, the role of intra-abdominal fat mass in the progress of atherosclerosis remains to be clarified. Methods: We evaluated visceral (VFA) and subcutaneous fat areas (SFA) by computed tomography and measured the plasma ADPN in 47 HD patients. We also examined the relationship between visceral fat accumulation and plasma ADPN levels and clinical parameters related to atherosclerosis. Results: Plasma ADPN was 29.0 ± 12.5 µg/ml in HD patients (mean ± SD), two-fold higher than that in control subjects (14.0 ± 9.1 µg/ml). Plasma ADPN correlated significantly and negatively with visceral fat area (VFA) (r = –0.49, p < 0.001) and subcutaneous fat area (SFA) (r = –0.42, p < 0.01) in HD patients. Plasma ADPN also correlated significantly and positively with HDL-cholesterol (r = 0.45, p < 0.005) and significantly and negatively with atherosclerotic index (AI, r = –0.39, p < 0.01) and triglycerides (r = –0.32, p < 0.05) in HD patients. Multiple stepwise regression analysis identified VFA as a significant independent predictor of plasma ADPN concentration in HD patients. Conclusion: Our findings indicate that visceral fat is a major determinant of plasma ADPN level, suggesting that visceral fat accumulation might be closely associated with the progression of atherosclerotic vascular disease in HD patients.

Coenzyme Q10 Administration Suppresses both Oxidative and Antioxidative Markers in Hemodialysis Patients

Background: Increased oxidative stress is associated with various complications in hemodialysis (HD) patients. Methods: We examined the effect of coenzyme Q10 (CoQ10) administration on the plasma oxidative products and antioxidant capacity in 36 HD patients for 6 months. Results: The advanced oxidation protein products (AOPP), malondialdehyde and the percentage of ubiquinone in total CoQ10 were significantly higher in HD patients than in healthy subjects before administration (0 month). Oxygen radical absorbing capacity (ORAC) and Trolox equivalent antioxidant capacity (TEAC), indicators of total antioxidant capacity, were also paradoxically higher in the HD patients at 0 month. AOPP and the percentage of ubiquinone significantly decreased during CoQ10 administration, but increased again after the discontinuation. ORAC and TEAC were also decreased during CoQ10 administration. Conclusion: The CoQ10 administration was partially effective for suppressing the oxidative stress in HD patients. The unexpected decrease of ORAC and TEAC by CoQ10 seemed to be associated with a decreased oxidative stress.

Impact of residual renal function on plasma levels of advanced oxidation protein products and pentosidine in peritoneal dialysis patients.

Background: Residual renal function (RRF) affects the survival rate and the development of cardiovascular disease in peritoneal dialysis (PD) patients. We evaluated the impact of RRF on oxidative and carbonyl stress in PD patients. Methods: Plasma advanced oxidation protein products (AOPP) and pentosidine were measured in PD patients with a urine volume of ≥300 ml/day (group A, n = 17) and <300 ml/day (group B, n = 14). AOPP and pentosidine were reevaluated after 12 months of follow-up in group A. Results: Plasma levels of AOPP and pentosidine in group A were significantly lower than those in group B. Renal creatinine clearance was inversely correlated with AOPP (p < 0.05) and pentosidine (p < 0.01). After 12 months of follow-up, no significant change was observed in AOPP and pentosidine in groups who maintained a urine volume of ≥300 ml/day, but significantly increased in groups whose urine volume decreased to less than 300 ml/day. There were significant inverse relationships between the changes in renal creatinine clearance and AOPP (p < 0.01) and pentosidine (p < 0.05). Conclusion: Loss of RRF is associated with increased plasma AOPP and pentosidine, indicating that preservation of RRF has a beneficial effect in reducing the oxidative and carbonyl stress in PD patients.

Impact of angiotensin II receptor blocker on plasma levels of adiponectin and advanced oxidation protein products in peritoneal dialysis patients.

Background: Oxidative stress and adipocytokines are reported to contribute to the pathogenesis of atherosclerosis. Though the inhibition of the renin-angiotensin system is known to have beneficial effects on atherosclerosis, the exact mechanisms for this remain to be clarified. The aim of this study was to determine the effects of angiotensin II receptor blockers (ARB) on the oxidative stress and adipocytokines in peritoneal dialysis patients. Methods: Candesartan (8 mg/day), an ARB, was administered for 3 months to 8 nondiabetic patients on peritoneal dialysis. Plasma levels of advanced oxidation protein products (AOPP) and adiponectin were measured before and 3 months after candesartan administration, and 3 months after discontinuation. Results: Plasma AOPP level decreased from 377.5 to 305.6 µmol/l (p < 0.05) following the administration of candesartan and returned to 394.6 µmol/l (p < 0.05) by 3 months after the discontinuation of the drug. Plasma adiponectin level increased from 12.5 to 18.8 µg/ml (p < 0.05) by candesartan and decreased again to 14.4 µg/ml (p < 0.05) after discontinuation. There was a significant inverse relationship between changes in plasma level of adiponectin and AOPP (r = – 0.888, p < 0.01). Conclusion: Candesartan increases plasma adiponectin level in association with the reduction of oxidative stress in peritoneal dialysis patients. Candesartan may be useful in preventing atherosclerosis in peritoneal dialysis patients.

The contribution of nitric oxide to renal vascular wall thickening in rats with l-NAME-induced hypertension

Abstractu2002We investigated the mechanisms of renal vascular wall thickening in a rat model of N-nitro L-arginine methyl ester (L-NAME)-induced hypertension. To separate the effects of L-NAME-induced hypertension from other effects of nitric oxide (NO) inhibition, we created two models of L-NAME-induced hypertension: both had the same blood pressure level but NO inhibition was moderate in one group (group M) and severe in the other (group S). Urinary excretion of nitrates and nitrites was lower in group S than in group M. Wall thickening and lipid deposition in renal vessels were significantly greater in group S than in groups M. Simple and multiple regression analyses indicated that renal vascular wall thickening was more strongly correlated with lipid deposition than with blood pressure. The number of vessels positive for staining with Sudan black B was negatively correlated with urinary NO excretion. Expression of fibronectin and transforming growth factor-β was greater in the Sudan black B-positive than in the Sudan black B-negative vessels, suggesting that extracellular matrix production was increased in vessels with lipid deposition. Lipid deposition and increased production of extracellular matrix may contribute to renal vascular wall thickening in L-NAME-induced hypertension. Some mechanisms independent of hypertension play important roles in vascular wall thickening induced by NO inhibition.

Association of serum total testosterone concentration with skeletal muscle mass in men under hemodialysis

PurposeAlthough skeletal muscle wasting can occur in chronic kidney diseases, its relationship with the serum testosterone concentration remains uncertain. This study investigates the relationship between serum testosterone and skeletal muscle mass in men under hemodialysis (HD).MethodsSixty men aged between 41 and 89xa0years undergoing HD for 15.0xa0±xa08.1xa0years were enrolled for this study. The muscle areas of the thigh (TMA) and abdomen (AMA) were measured by computed tomography (CT), and the association between these muscle areas and serum total testosterone was examined with adjustment of age and other nutritional variables.ResultsThe mean serum total testosterone in our HD patients (6.33xa0±xa02.90xa0ng/mL) was not lower than that of the Japanese general population, but showed a positive correlation with TMA (rxa0=xa00.39, pxa0<xa00.05), AMA (rxa0=xa00.52, pxa0<xa00.001), serum creatinine (rxa0=xa00.33, pxa0<xa00.05), and the creatinine generation rate (rxa0=xa00.26, pxa0<xa00.05). Serum total testosterone was inversely correlated with age (rxa0=xa0−0.32, pxa0<xa00.05), CRP (rxa0=xa0−0.31, pxa0<xa00.05), and IL-6 (rxa0=xa0−0.24, pxa0<xa00.05). A multiple-regression analysis showed both serum total testosterone and age to be an independent determinant of the muscle mass in these patients.ConclusionsThis study identified testosterone as a determinant of muscle mass in HD men.

Factors Involved in the Development of Hypertension Induced by a Low-Protein Diet in Rats with Renal Injury

Background/Aims: While a low-protein diet (LPD) has been reported to increase blood pressure, the mechanism for its increase has not yet been clarified. We investigated the factors involved in the development of hypertension induced by LPD in rats with post-cyclosporine (CsA) nephropathy, and determined the appropriate composition for LPD that is to be utilized for renal research. Methods: The rats were divided into 4 groups, each group being fed either a normal-protein diet (NPD), LPD with a low sucrose content as the main component of carbohydrate, LPD with a high-sucrose content, or LPD with low sucrose plus 2% L-arginine (Arg) for 12 weeks, and the blood pressure, urinary nitric oxide (NO) metabolite (NOx) excretion, renal NO-generating capacity and renal Arg content were compared among these groups. CsA was administered for the first 5 weeks to all groups. Results: The blood pressure was significantly higher in the high-sucrose LPD rats than in the NPD and the low-sucrose LPD rats. The supplement of Arg significantly decreased the blood pressure in the low-sucrose LPD rats. Urinary NOx, renal NO-generating capacity and the renal Arg content were significantly lower in the low-sucrose LPD rats than in the NPD rats. Arg supplementation to the LPD rats returned these values to the level of the NPD rats. Conclusion: The increase in blood pressure by LPD was associated with the higher amount of sucrose contained in LPD and the decrease in NO generation caused by the Arg depletion in rats with post-CsA nephropathy. For animal experiments we recommend that sucrose should not be used in LPD to balance the energy intake between LPD and NPD, and that a small amount of Arg be supplemented to LPD.