Clinical evaluation of AK 100 ULTRA for predilution HF with on-line prepared bicarbonate substitution fluid. Comparison with HD and acetate postdilution HF.

Convective transport across dialysis membranes has been known for a long time to be a good alternative to diffusion. Predilution hemofiltration (HF) offers a better clearance of small molecules and overcomes the blood viscosity problems related to conventional postdilution HF treatment. Three patients have performed a total of 293 predilution HF treatments with AK 100 ULTRA. The bicarbonate substitution fluid has been prepared on-line by the machine. The treatments have been well tolerated and no adverse patients reactions related to the quality of the substitution fluid or the predilution HF treatment have been observed. There is a drop in creatinine for all patients indicating an improved creatinine clearance. Bicarbonate predilution HF has been shown to be a safe and efficient treatment modality, it offers the possibility to improve the cardiovascular stability of patients having problems with other treatment modalities an it offers an improved intertreatment well-being for the patients.

Effect of a new model of hemodialysis potassium removal on the control of ventricular arrhythmias.

The primary aim of this multicenter, prospective, randomized cross-over study was to clarify whether a new model of hemodialysis (HD) potassium (K) removal using a decreasing intra-HD dialysate K concentration and a constant plasma-dialysate K gradient (treatment B) is capable of reducing the arrhythmogenic effect of standard HD, which has a constant dialysate K concentration and decreasing plasma-dialysate K gradient (treatment A). The secondary aim was to verify whether this new model is clinically safe. In treatment B, the initial dialysate K concentration had to be 1.5 mEq/liter less than the plasma K concentration, and exponentially decrease to 2.5 mEq/liter at the end of HD. Forty-two chronic HD patients with an increase in premature ventricular complexes (PVC) during dialysis were enrolled from 18 participating centers, and randomly assigned to either sequence 1 (ABA) or sequence 2 (BAB). A pool of 333 of 378 expected ECG Holter recordings were checked for signal quality; 269 (71%) from 36 patients (86%) had a satisfactory signal quality and 108 were selected for analysis (1 per patient per period). There was a difference in the natural logarithm of the increase in PVC/hr and PVC couplets/hr during HD between treatments A and B (1.70 +/- 1.59 vs. 1.09 +/- 1.76 and 0.94 +/- 0.86 vs. 0.64 +/- 1.01, a reduction of 36% and 32%, P = 0.011 and 0.047, respectively) without any carry over effect (P = 0.61 and 0.24, respectively). The fact that this decrease of one third is due to a lower plasma-dialysate K gradient is supported by the observation that it was more evident during the first than the last two hours of HD (a reduction in the natural logarithm of the increase in PVC/hr and PVC couplets/hr of 60% and 60%, P 0.002 and 0.009, vs. 26% and 17%, P = 0.098 and 0.332, respectively): the initial plasma-dialysate K gradient was 2.3 times lower during treatment B than during treatment A, without adversely affecting pre-HD plasma K levels. These results could have a considerably clinical impact not only because of the possibility of physiologically decreasing the arrhythmogenic effect of HD, but also because this effect can be considered a "marker" of the electrophysiological derangement induced by the administration of standard HD three times a week for years ("electric disequilibrium syndrome").

Hemodialysis using a constant potassium gradient: rationale of a multicenter study.

The aim of this study is to evaluate the relationship between two different procedures for potassium removal during hemodialysis (HD) and cardiac arrhythmias. Cell excitability and the transmission of impulses may be influenced by variations of resting membrane potential (RMP). The rapid decrease of plasma potassium during the first two hours of standard HD causes a membrane hyperpolarization. A different K+ kinetic, with a gradual and constant elimination of K+ during HD, may reduce this further unphysiological aspect and its clinical consequences. This can be obtained keeping blood-dialysate K+ gradient as constant as possible with the use of a dialysate K+ concentration (Kd) decreasing during HD. Our experimental studies on various K+ intradialytic gradients seem to indicate as optimal to this purpose K+ gradients of 1.5 mEq/l at the beginning of dialysis, esponentially decreasing during treatment to Kd values of 2.5 mEq/l at the end of dialysis (variable Kd). Patients included in the trial will be submitted to two different methods of treatment with Kd 2 mEq/l and variable Kd, and to a 24 hours ECG the day of dialysis. We will compare the number of intra and interdialytic premature ventricular complexes to evaluate the impact of two different models of potassium removal on arrhythmias.

Forecasting correct sodium balance in hemodiafiltration procedures involving infusions.

Four patients, stable on acetate hemodialysis (AHD), were switched to acetate-free biofiltration (AFB) which differs from AHD and bicarbonate hemodialysis (BHD) in that the dialysate contains no buffer, which is given intravenously as a hypertonic (1/6 M) Na bicarbonate solution. Within the 1st month the patients developed thirst and hypertension attributed to a positive Na balance. The aim of this investigation was to check this (1) by a study based on the predictable changes induced in the body compartments of 13 patients by the infusion and ultrafiltration (UF) of a hypertonic solution and (2) by direct determination and calculation of 28 Na mass balances in BHD and AFB. The theoretical model indicated that infusion of 4.87 liters of a 166.7 mEq/l Na bicarbonate solution and UF of the same amount caused a positive balance of 233 mosm of Na. The Na mass balances showed a relationship between Na transmembrane gradient and loss or gain of Na in both methods (p less than 0.0001). The slopes of the regression lines were not significantly different but there was a highly significant difference between the y axis intercepts (p less than 0.0001), which indicates that the same Na transmembrane gradient that gives no net change of Na in BHD, induces a net gain of 240 mosm (120 mEq of Na) in AFB and that to obtain the same Na balance dialysate Na should be reduced by about 8 mEq/l in AFB. These data are the same as the theoretical forecast which could be extended to all hemodiafiltration methods in which solutions of any tonicity have to be infused, in order to correctly predict the Na balance.

Kelfiprim versus co-trimoxazole in recurrent and persistent urinary tract infections: multicenter double-blind trial.

Kelfiprim (KP) is a new bactericidal agent containing trimethoprim (T) and sulfametopyrazine (S), a long-acting sulfonamide (ratio 5:4). The posology is one capsule (T 250 mg + S 200 mg) daily, after a loading dose of two capsules on the first day. To evaluate the clinical value of Kelfiprim (KP) vs co-trimoxazole (CO) in urinary tract infection (UTI) a controlled multicenter double-blind trial (MDBT) was carried out in 76 patients suffering from persistent and recurrent UTIs. About 90 per cent response rate (sterile urine at the end of treatment) was obtained for KP and about 85 per cent for CO in recurrent UTI. In persistent UTI the rate of recovery was 66.8 per cent and 53 per cent for KP and CO, respectively. Safety of treatments was excellent in 97 per cent of patients treated with Kelfiprim and 87 per cent treated with co-trimoxazole. Two patients, one in each group, were dropped from the study because of adverse reactions.

Controlled trial of methylprednisolone and chlorambucil in idiopathic membranous nephropathy.

Sixty-seven adults with idiopathic membranous nephropathy and the nephrotic syndrome were randomly assigned to symptomatic treatment only or to a six-month course of methylprednisolone alternated with chlorambucil every other month. Patients were followed for one to seven years. At the end of follow-up (mean of 31.4 +/- 18.2 months for the treated group and 37.0 +/- 22.0 for the control group) 23 of 32 treated patients were in complete or partial remission, as compared with 9 of 30 control patients (P = 0.001). Twelve of the treated patients were in complete remission, as compared with only two of the controls. In the treated group there were no changes in renal function during follow-up, whereas in the control group the reciprocal of the plasma creatinin level, which is proportional to the creatinine clearance, decreased significantly (P = 0.00017) after two years of follow-up. Side effects were minimal in all treated patients except two, who were dropped from the study because of peptic ulcer and gastric intolerance to chlorambucil. We conclude that steroid and chlorambucil treatment for six months favors remission of the nephrotic syndrome in adults with idiopathic membranous nephropathy and can preserve renal function for at least some years.

Controlled trial of monthly alternated courses of steroid and chlorambucil for idiopathic membranous nephropathy.

Forty-nine patients with membranous nephropathy (MN) and nephrotic syndrome (NS) were randomly allocated to supportive or specific therapy. The latter consisted of steroids or chlorambucil given in alternate months for a cumulative period of six months. Three patients in the experimental group were dropped from the study because of therapy related side-effects. At the end of follow-up there were significantly more patients in complete or partial remission in the experimental group than in the controls. The mean serum creatinine did not change in treated patients, but it significantly increased in controls.

[Potassium removal: a factor limiting the correction of acidosis during dialysis]. / La soustraction potassique: facteur limitant la correction de l'acidose pendant la dialyse.

The diffusional fluxes of urea, potassium and bicarbonate across the dialytic membrane (external balance), and across the cellular membrane (internal balance), were determined in 7 patients in haemodialysis using potassium free dialysate and dialysate containing 2.0 mEq/1 of potassium. The results obtained show an inverse correlation between extraction of potassium and intake of bicarbonate in both external and internal balance. This is probably due to the increase in membrane electrical potential resulting from a fall in blood potassium and emphasizes the importance of electrical driving forces in diffusional fluxes across cellular membranes.

Potassium removal as a factor limiting the correction of acidosis during dialysis.

The diffusional fluxes of urea, potassium and bicarbonate across the dialysis membrane (external balance) were determined in seven patients during haemodialysis using potassium free dialysate and dialysate containing 2.0mEq/L of potassium. The results show an inverse correlation between extraction of potassium and intake of bicarbonate in both external and internal balances. This is probably due to the increase in cell membrane electrical potential resulting from a fall in blood potassium and emphasises the importance of electrical driving forces in diffusional fluxes across cellular membranes.

Hemodialysis with "adequate" sodium concentration in dialysate.

This investigation was undertaken to define the "adequate" sodium concentration in the dialytic fluid allowing to maintain a stable plasma effective osmolality during dialysis. Isonatric dialysate is shown to miss this aim by inducing a predictable postdialytic hypernatremia. To avoid this effect a new approach was made. 17 clinically stabilized patients, previously dialyzed over a period of at least 2 years with a dialysate sodium concentration of 133 mEq/l, underwent dialysis with the "adequate" sodium concentration in the dialysate for over 3 years. During dialysis cramps, headache, hypotension, hypertensive crises and postdialytic weakness were reduced in frequency and nearly disappeared. No deterioration in blood pressure control occurred and improvement in some general parameters (hematocrit, glucose and insulin metabolism, well-being) was reported after prolonged treatment.