Improved left ventricular contractility with cool temperature hemodialysis

Improved left ventricular contractility with cool temperature hemodialysis. Cool temperature dialysis (CTD) has been shown to sharply decrease the frequency of intradialytic hemodialysis hypotension, but the mechanism of this hemodynamic protection is unknown. Therefore, we performed two-dimensional echocardiographic studies of left ventricular contractility in six stable hemodialysis patients before and after hemodialysis at 37°C (RTD) and 35°C (CTD). Left ventricular function was assessed by plotting the rate-corrected velocity of circumferential fiber shortening (Vcfc) against end-systolic wall stress (σes) at four different levels of afterload. Linear regression was used to calculate Vcfc at a common afterload of 50 g/cm2. Changes in weight and dialysis parameters were similar following RTD and CTD. Mean arterial pressure and heart rate did not change significantly following RTD or CTD. The Vcfc – σes relation was shifted upward in each patient after CTD, indicating increased contractility as compared to RTD or pre-dialysis baseline. Pre-dialysis Vcfc at an afterload of 50 g/cm2 was similar during RTD and CTD (0.94 ± 0.24 circ/sec vs. 0.92 ± 0.22 circ/sec). Post-dialysis Vcfc at an afterload of 50 g/cm2 was significantly higher for CTD than for RTD (1.13 ± 0.29 circ/sec vs. 0.98 ± 0.30 circ/sec, P = 0.0004). Thus, cool temperature dialysis increases left ventricular contractility in hemodialysis patients, which may be a potential mechanism whereby hemodynamic tolerance to the dialysis procedure is improved

Calcium citrate, a nonaluminum-containing phosphate-binding agent for treatment of CRF

Calcium citrate, a nonaluminum-containing phosphate-binding agent for treatment of CRF. Calcium citrate was evaluated as a dietary phosphate binder in 81 patients with end-stage renal disease. These patients were grouped as follows: Group 1, 43 patients who were treated with calcium citrate; and Group 2 (the control group), 38 patients who were treated with aluminum-containing compounds. Blood chemistries were measured monthly and medications adjusted to maintain the following levels: serum calcium, >9 mg/dl; serum phosphorus, < 5.5 mg/dl; and total CO2 content, >22 mmol/liter. At the end of the treatment period, the following serum values were obtained in Groups 1 and 2, respectively: calcium, 9.6 ± 1.2 mg/dl (mean ± SD) versus 8.9 ± 0.8 mg/dl (P < 0.001); phosphorus, 5.5 ± 1.9 mg/dl versus 7.0 ± 2.3 mg/dl (P < 0.005); and calcium-phosphate product, 52 ± 18 versus 61 ± 21 (P < 0.05). Differences in alkaline phosphatase, total CO2 content, and C-terminal parathyroid hormone (C-PTH) values were not statistically significant between the two groups. Fifteen patients in Group 1 were then switched to aluminum-containing compounds and chemistries were compared one month later. During calcium citrate therapy, serum calcium was significantly higher, while C-PTH and serum alkaline phosphatase were significantly reduced. No difference was noted in serum phosphorous and total CO2 content. A questionnaire completed by 17 patients in Group 1 documented excellent patient tolerance to calcium citrate. Hypercalcemia (>10.5 mg/dl) was the only significant complication, but only one patient became symptomatic. We conclude that, as a phosphate binder, calcium citrate is at least as effective as aluminum-containing compounds

Loss of β Epithelial Sodium Channel Function in Meibomian Glands Produces Pseudohypoaldosteronism 1–Like Ocular Disease in Mice

Human subjects with pseudohypoaldosteronism-1 because of loss-of-function mutations in epithelial sodium channel (ENaC) subunits exhibit meibomian gland (MG) dysfunction. A conditional βENaC MG knockout (KO) mouse model was generated to elucidate the pathogenesis of absent ENaC function in the MG and associated ocular surface disease. βENaC MG KO mice exhibited a striking age-dependent, female-predominant MG dysfunction phenotype, with white toothpaste-like secretions observed obstructing MG orifices at 7 weeks of age. There were compensatory increases in tear production but higher tear sodium and indexes of mucin concentration in βENaC MG KO mice. Histologically, MG acinar atrophy was observed with ductal enlargement and ductal epithelial hyperstratification. Inflammatory cell infiltration was observed in both MG and conjunctiva of βENaC MG KO mice. In older βENaC MG KO mice (5 to 11 months), significant ocular surface pathologies were noted, including corneal opacification, ulceration, neovascularization, and ectasia. Inflammation in MG and conjunctiva was confirmed by increased cytokine gene and protein expression and positive Ly-6B.2 immunostaining. Cell proliferation assays revealed lower proliferation rates of MG cells derived from βENaC MG KO than control mice, suggesting that βENaC plays a role in cell renewal of mouse MG. Loss of βENaC function resulted in MG disease and severe ocular surface damage that phenocopied aspects of human pseudohypoaldosteronism-1 MG disease and was sex dependent