Velocity recovery cycles of human muscle action potentials in chronic renal failure.

OBJECTIVE: To test the hypothesis that muscle fibers are depolarized in patients with chronic renal failure, by measuring velocity recovery cycles of muscle action potentials as indicators of muscle membrane potential. METHODS: Velocity recovery cycles were recorded from brachioradialis muscle by direct muscle stimulation in 13 patients, before, immediately after, and 1h after haemodialysis, and compared with those from 10 age-matched controls. RESULTS: In the patients, supernormality was reduced by 47%, and relative refractory period increased by 60.5% compared with controls (both P<0.001). Dialysis normalized the supernormality, but an hour later it was again reduced. These changes in supernormality were strongly correlated with the changes in serum potassium levels (P<0.0001). A late component of supernormality, attributed to potassium accumulation in the t-tubule system, was also reduced in the patients but remained abnormally low after dialysis. CONCLUSIONS: Muscle membranes in the patients were chronically depolarized by hyperkalemia. Whereas dialysis transiently normalized muscle membrane potential, it was not adequate to normalize t-tubule function. SIGNIFICANCE: Chronic muscle membrane depolarization by hyperkalemia may account for some of the functional deficits in uremic myopathy. Consistent normalization of membrane potential by avoiding hyperkalemia may therefore reduce symptoms of 'uremic myopathy'.

Intermediate outcome and risk factor assessment of bovine vascular heterografts used as AV-fistulas for hemodialysis access.

OBJECTIVES: This observational study was set up to prospectively follow all bovine heterograft (ProCol) fistulas implanted for hemodialysis access between 1998 and 2002. METHODS: ProCol was implanted if autogenous vein was not available or if patients presented with a history of failed, infected or otherwise complicated ePTFE grafts and/or on immunosuppressive therapy. Fistula patency was the primary outcome; secondary outcomes were clinical events and the rate of access revisions. RESULTS: Sixty-two ProCol grafts were implanted in 56 patients. The mean primary (PP) and secondary patency (SP) was 334 (SEM 57) and 528 (SEM 59) days, respectively. Coronary heart disease was associated with a significantly better SP (OR 0.2, 95% CI 0.1-0.9) whilst diabetes mellitus was associated with a significantly worse SP (OR 0.2, 95% CI 0.1-0.9). Reinterventions were performed at a mean rate of 1.23 (SEM 0.17) per fistula. The relative risk of access revision was significantly higher in patients with diabetes mellitus (OR 9.2, 95% CI 2.3-37.2). CONCLUSIONS: ProCol grafts, used for AV-fistulas, demonstrate acceptable patency rates in high-risk haemodialysis patients. Diabetes mellitus jeopardizes the patency of these fistulas and is associated with a high revision rate.

Differential subcellular localization of ENaC subunits in mouse kidney in response to high- and low-Na diets.

Previous electrophysiological experiments on renal cortical collecting ducts indicated that dietary sodium intake and variations in aldosterone plasma levels regulate the abundance of functional epithelial Na channels (ENaC) in the apical plasma membrane. In mouse kidney we investigated by immunohistochemistry whether feeding for 3 wk a diet with high (3% Na) and low (0.05% Na) Na content influences the distribution pattern of ENaC. In mice of all experimental groups, ENaC was apparent in cells from the late portion of the distal convoluted tubule (DCT2) down to the medullary collecting duct (CD). In mice on a high-Na diet (plasma aldosterone: 40.8 +/- 2.0 ng/dl), the alpha-subunit was undetectable, and the beta- and gamma-ENaC were detected in the cytoplasm, but not in the apical plasma membrane of the cells. In contrast, in mice on a low-Na diet (plasma aldosterone: 93.6 +/- 9.3 ng/dl) all three ENaC subunits were displayed in the subapical cytoplasm and in the apical membrane of DCT2, connecting tubule (CNT), and, although less prominent, in cortical CD cells. Apical plasma membrane immunostaining progressively decreased along the cortical CD, simultaneously with increasing cytoplasmic staining for beta- and gamma-ENaC. Thus our data on mice adapted to moderately low and high Na intake suggest that regulation of ENaC function in vivo involves shifts of beta- and gamma-subunits from the cytoplasm to the apical plasma membrane and vice versa, respectively. The insertion of these subunits into the apical plasma membrane coincides with upregulation of the alpha-subunit and its insertion into the apical plasma membrane.