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Almost every dialysis patient has underlying cardiac disease, placing them at risk for cardiac death. The QT interval (a measure of repolarization) is often prolonged in dialysis patients and has been found to be a predictor of sudden death as well as for the QT dispersion. Recently, a prolonged PCA-T (> 0.246 for men and > 0.320 for women) applied to 12-lead recordings is found to predict three year mortality in the general population (Okin et al 2002). The aim of this retrospective study was to explore the predictive value of PCA-T for all-cause and cardiac mortality in hemodialysis (HD) patients. We analyzed data from 164 patients (67 women and 97 men) in whom digital ECG recordings were available from previous clinical studies. Standard 12-leads Holter ECGs (H-12 Holter, Mortara Instrument Inc.) were recorded starting 10 minutes before the dialysis session and lasting for at least 4 hours. A median value of PCA-T was computed for each patient throughout the whole ECG recording. The optimal threshold for PCA-T was defined by ROC analysis as 0.366 in women (accuracy= 0.88) and as 0.320 in men (accuracy= 0.76). Deaths were classified as cardiac if caused by myocardial infarction, sudden death from CHD, or congestive heart failure. After a follow-up of 2 years, patients were censored as dead or alive considering the days from the date of the ECG recording. Patients were then divided in two groups depending on the median PCA-T value respect to the above thresholds. Endpoints were all-cause (ACM) and cardiac (CM) mortality. Survival was computed by the Kaplan-Meier analysis (significant if p

Fabry disease (FD) is a rare X-linked disorder characterized by low or absent activity of the lysosomal enzyme α-glycosidase-A that leads to progressive accumulation of glycosphingolipids in different organs and tissues. Clinical manifestations vary from classic to atypical forms characterized by one prevalent organ involvement, and a renal variant has been described in men but not in women. However, little is known about renal manifestation in females affected by FD. We herein report a case of a 22-year-old female with isolated and persistent microalbuminuria as the only sign of FD. In light of the importance of early recognition and treatment of FD organ damage, this case should call for future studies to determine how to assess organ damage, investigate the existence of a 'renal variant' in FD female patients and determine when best to start enzyme replacement therapy (ERT).

Background Low and high dialysate calcium (Ca2+) content may have positive and harmful effects depending on the considered pathological aspect: hemodynamic instability, cardiac arrhythmias, parathormone release, adynamic bone disease, cardio-vascular calcifications. We hypothesized that a time-profiled Ca2+ concentration would keep the cardiovascular advantages of high Ca2+ but would reduce the risk of calcium overload. Methods A prospective, multicenter study using a particular hemodiafiltration technique that allows the profiling of electrolytes was designed. Patients (n = 22) underwent randomly a 3-week dialysis session with low and high constant dialysate Ca2+ (LdCa, 1.25 mM and HdCa, 2 mM) and profiled Ca2+ (PdCa), respectively. Plasma and spent dialysate Ca2+, systolic and diastolic arterial pressure (SAP, DAP) and QT interval corrected for heart rate (QTc) were analyzed. Results Plasma Ca2+ concentration decreased in LdCa, whereas it increased in HdCa and to a lesser extent, in PdCa. Total amount of Ca2+ given to the patient in PdCa (15.5 ± 1.0 mmol) was higher than in LdCa (4.3 ± 1.6 mmol) but lower than in HdCa (21.9 ± 3.3 mmol). SAP and DAP decreased in LdCa, whereas it was almost constant in both HdCa and PdCa. QTc significantly increased, up to critical values (>460 msec), only during LdCa. Conclusions PdCa seems to retain the advantages of high Ca2+ in terms of hemodynamic stability and modification of QTc while reducing the excessive positive calcium balance typical of dialysis with high Ca2+ content.

Background In Fabry disease, end-stage renal disease (ESRD) and severe neurologic and cardiac complications represent the leading causes of late morbidity and mortality. A comprehensive Italian nationwide survey study was conducted to explore changes in cardiac status and renal allograft function in Fabry patients on renal replacement therapy (RRT) and enzyme replacement therapy (ERT). Methods This study was designed as a cross-sectional survey study with prospective follow-up. Of the 34 patients identified via searches in registries, 31 males and 2 females who received RRT and ERT (agalsidase beta in 30 patients, agalsidase alpha in 3) were included. Left ventricular mass index (LVMI), interventricular septal thickness at end diastole (IVSD), left ventricular posterior wall thickness (LVPWT) and renal allograft function were assessed at ERT baseline and subsequently at yearly intervals. Results The patients in the dialysis and transplant groups had been started on dialysis at age 42.0 and 37.1 years (mean), respectively, and patients in the transplant group received their renal allograft at age 39.8 years (mean). The mean age at the start of ERT was similar, 44.1 and 44.6 years, respectively. The mean RRT follow-up was 61.1 and 110.6 months for dialysis and transplant patients, respectively, whereas the ERT duration was 45.1 and 48.4 months, respectively. Cardiac parameters increased in dialysis patients. In transplant patients, mean LVMI seemed to plateau during agalsidase therapy at a lower level as compared to baseline. Decline in renal allograft function was relatively mild (-1.92 ml/min/year). Agalsidase therapy was well tolerated. Serious ERT-unrelated events occurred more often in the dialysis group. Conclusions Kidney transplantation should be the standard of care for Fabry patients progressing towards ESRD. Transplanted Fabry patients on ERT may do better than patients remaining on maintenance dialysis. Larger, controlled studies in Fabry patients with ESRD will have to demonstrate if ERT is able to change the trajectory of cardiac disease and can preserve graft renal function.

BACKGROUND: Although sudden death is one of the most frequent causes of death in haemodialysis (HD) patients, the problem of cardiac arrhythmias, the major cause of these outcomes, has been little discussed. METHODS: In 30 arrhythmia-prone HD patients, we compared the arrhythmogenic effects of two dialysis techniques differing in dialysate potassium (K) content. Each patient underwent Acetate-Free Biofiltration sessions with constant (2.5 mEq/l) K (AFB) and sessions with decreasing intra-HD K (AFBK), according to a crossover single blind design. Holter ECG recording and plasma electrolyte measurements were performed during each dialysis session. RESULTS: There was a tendency in the whole sample for arrhythmia appearance in AFBK to be reduced as compared to AFB throughout the 24 hr period, although this reduction was not statistically significant. In the subset of patients sensitive to dialysis as far as arrhythmia onset is concerned, AFBK was systematically less arrhythmogenic than AFB (P < 0.01). The highest difference was achieved around the 14th hour after the end of dialysis, when the premature ventricular contractions in AFB were 3.9 times higher than in AFBK (P < 0.05). Potassium kinetics differed between the two procedures. At the first hour of treatment, the plasma K concentration was lower in AFB than in AFBK (3.67 +/- 0.15 mEq/l in AFB vs 4.06 +/- 0.13 mEq/l in AFBK, P = 0.05). CONCLUSIONS: Our study shows a greater arrhythmogenic activity with the use of a constant and relatively low K concentration as compared to decreasing K profiling in dialysis-sensitive arrhythmic patients. Smoother K removal may well engender a kind of protective effect.

A therapy-specific worsening of cardiovascular stability during bicarbonate dialysis (BD) with respect to acetate-free biofiltration (AFB) have been previously reported. We further investigated the impact of the 2 therapies on electrocardiographic parameters in order to gain novel insight into the cardiac responses. Holter ECG acquired during hypotension-free sessions (12 BD + 12 AFB) were retrospectively analyzed. R-R intervals were extracted from ECG recordings. An autoregressive spectral technique was used to compute low- and high-frequency (LF and HF) components of heart rate variability (HRV). QT interval duration was measured with a computer-assisted technique and corrected for HR. In BD the LF component of HRV after an initial increase was slowly depressed with respect to AFB (p < 0.05). QT duration showed a significant (p < 0.01) hemodialysis-induced reduction. QT shortening was more pronounced (p < 0.05) in BD than in AFB (-31 vs. -10 ms), even after correction for HR (p < 0.05). Cardiac electrical activity is significantly affected by the hemodialysis technique. The decrease in the LF component of HRV and the QT shortening are coherent with the worse cardiovascular tolerance observed in BD and with the hypothesis of an enhanced production of endogenous nitric oxide.

Model-based study of the effects of the hemodialysis technique on the compensatory response to hypovolemia.BackgroundHemodialysis technique (dialysate composition, filter, convection/diffusion ratio, etc.) can have an impact on the patient's tendency to acute hypotension. We have examined the hypothesis that the dialysis technique affects the hypotension risk by altering the cardiovascular compensatory response to hemodialysis-induced hypovolemia.MethodsTwelve hypotension-prone subjects were studied during six sessions of conventional bicarbonate dialysis (BD) and six sessions of acetate-free biofiltration (AFB). Blood volume (BV) control system was used in AFB to provide a BV change equivalent to the BV change observed in BD. The efficacy of reflex compensatory mechanisms was assessed by a model-based computer analysis of the BD and AFB sessions.ResultsBD sessions were complicated by hypotension more frequently than the AFB ones (34/66BD vs. 18/66AFB). Hypotension arose about 60 minutes earlier in BD (123 ± 41 minutes in BD vs. 183 ± 25 minutes in AFB, P < 0.01), and after a smaller BV reduction (hypotension BV 7.9%± 2.0% in BD vs. 10.9%± 2.6% in AFB, P < 0.05). Model-based computer analysis of the sessions without hypotension revealed differences in peripheral resistance adaptation (9%± 9% BD vs. 19%± 7% AFB, P < 0.05) as well as in the stroke volume reduction (19%± 8% BD vs. 10%± 8% AFB, P < 0.001). Model analysis of sessions with hypotension indicated that compensatory mechanisms were almost inoperative in BD, whereas a residual capacity to control peripheral resistance and cardiac contractility was present in AFB. Model simulations demonstrated that hypotension occurred later in AFB since the residual compensatory capacity in AFB was able to sustain the arterial pressure for larger BV reductions (8.3% BD vs. 11.2% AFB).ConclusionThe increased risk of acute hypotension in BD compared to AFB is caused by a therapy-induced inhibition of reflex compensatory response to hypovolemia.