Protein-energy wasting (PEW), defined as a loss of body protein mass and fuel reserves, is a powerful predictor of adverse outcomes in haemodialysis (HD) patients. Robust arguments suggest that intra-dialytic exercise, combined with oral/parenteral nutrition, enhances the effect of nutritional interventions in HD patients. This pilot randomized controlled trial investigated the feasibility and the effects of a 6 month intra-dialytic cycling program combined to a nutritional support on PEW, physical functioning (gait, balance, muscle strength) and quality of life (QoL) in older HD patients (mean age 69.7 ± 14.2 years).Twenty-one patients fulfilling diagnostic criteria of PEW were randomly assigned to Nutrition-Exercise group (GN-Ex , n = 10) or Nutrition group (GN , n = 11). Both groups received nutritional supplements in order to reach recommended protein and energy intake goals. In addition GN-Ex completed a cycling program. No significant difference between groups was found in the number of patients having reached remission of PEW. Likewise, no change was observed in serum-albumin, -prealbumin, C-reactive protein, body mass index, lean- and fat-tissue index, or quadriceps force. Interestingly, we found positive effects of exercise on physical function and QoL for the GN-Ex , as evidenced by a significant improvement in the 6-min walk test (+22%), the absence of decline in balance (unlike the GN ), and a noteworthy increase in QoL (+53%). Combining intra-dialytic exercise and nutrition in HD patients is feasible, and well accepted, improves physical function and QoL but it appears not to have the potential to reverse PEW.
Impaired vascular reactivity during combined ultrafiltration-hemodialysis (UF+HD) compared with hemofiltration (HF) remains a rather enigmatic problem, the causes of which are still not well understood. Although a number of factors have been claimed to be responsible, most recent studies point to a major role of the extracorporeal blood temperature, which is usually lower during HF compared with UF + HD. However, previous studies in which hemodynamics were studied during UF + HD and HF in relation to the extracorporeal blood temperature are limited by the use of acetate in UF + HD, and measurements were often confined to BP and heart rate. Therefore, arterial BP, as well as forearm vascular resistance (FVR) and venous tone (strain-gauge plethysmography), was measured in 11 hemodialysis patients during 3 h UF + HD (37.5 degrees C) and predilution HF (39.0 degrees C = warm HF), resulting in equivalent extracorporeal blood temperatures. Patients were also studied during cold HF at an infusate temperature of 36.0 degrees C. UF + HD and HF were matched with respect to the dialysate and infusate composition (bicarbonate), bio-compatibility factors, and small molecule clearance. At equivalent temperatures, UF + HD and HF were associated with a comparable vascular and BP response. Only cold HF was associated with a significant increase in FVR. In addition, FVR and venous tone, as well as arterial BP, were all significantly higher during cold HF compared with both UF + HD and warm HF. These results indicate that the disparity in vascular reactivity between UF + HD and HF is primarily related to differences in the extracorporeal blood temperature.
The acute renal effects of neutral endopeptidase 24.11 (E-24.11) inhibition induced by a single oral dose of sinorphan (100 mg) were investigated in 10 healthy normotensive subjects on normal sodium diet. Sinorphan inhibited 90% of E-24.11 activity and increased plasma atrial natriuretic peptide (ANP) and urinary guanosine 3',5'-cyclic monophosphate (cGMP) by 70 and 100%, respectively. Sinorphan increased urinary sodium output by 50% (P < 0.001) and decreased fractional distal reabsorption by 4% (P < 0.01). Sinorphan increased glomerular filtration rate (GFR) and filtration fraction by 10% 1 h after administration and decreased renal plasma flow by 10%. Mean arterial pressure, renal vascular resistance, plasma aldosterone concentration, and renin activity were unmodified. Sinorphan decreased fractional clearance of neutral dextrans over the 34- to 52-A radius range. Applying the changes along with a hydrodynamic isopore with shunt model, sinorphan significantly increased capillary pressure gradient (delta P; 39 +/- 1 vs. 34 +/- 1 mmHg; P < 0.01), whereas ultrafiltration coefficient was unchanged. In conclusion, endopeptidase inhibition increased endogenous plasma ANP and cGMP generation and induced natriuresis through both an increase in filtered load and a decrease in distal tubular reabsorption of sodium. Sinorphan increases GFR, filtration fraction, and delta P, probably through an increase in efferent over afferent arteriolar resistance ratio.
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