Hydroelectrolytic equilibrium change in dialysis.

Hydroelectrolytic equilibrium alteration in dialysis patients before dialytic treatment consists in extracellular volume expansion and hyperkalemia. Extracellular volume expansion is due to salt and water retention. Because of the self-regulation phenomenon of cell volume, it is made prevalently at the expense of extracellular volume. Hyperkalemia derives not only from alimentary K+ retention but, above all, from the K+ intracellular transfer into extracellular volume for tamponage of acid load, owing to the same selfregulation of cell volume and to the reduction of Na+/K+ pump activity with a subsequent change in Ki/Ke ratio. Dialysis must reduce expanded extracellular volume without inducing osmolar changes. To do this, salt and water removal must occur by ultrafiltration. Moreover, it is necessary to define Na+ concentration in dialysate or in reinfusion solution able to undo, by diffusion, the plasmatic Na+ increase due to Donnan effect. K+ dialytic removal presents the problem of defining the K+ quantity to be removed: K+ fecal excretion is increased in the uremic patient and there is no correlation between the quantity of K+ removed and successive increase of kalemia. K+ removal occurs by diffusion according to the concentration gradient between plasma and dialysate through dialytic membrane. The reduction of kalemia determines, in its turn, diffusion fluxes according to the concentration gradient of intracellular K+ towards extracellular volume. Because the electrical membrane potential at rest (REMP) is due to K+ fluxes for passive transmembrane diffusion, the increase of these fluxes causes REMP increase. Cardiac activity expresses this change with the appearance of intradialytic arrhythmia. The use of a dialysate with K+ concentration that decreases during dialysis in line with K+ rate (variable K+) reduces the arrhythmias induced by dialysis. The quantity of K+ removed with this procedure is the same as that obtained by using a dialysate with K K+ constant concentration of 3 mEq/l, but the percentage removed from intracellular volume is lower with improvement of Ki/Ke ratio. The influence of intradialytic REMP increase linked to K+ removal also concerns the correction of metabolic acidosis: the acquired bicarbonate during dialysis increases on reducing removal K+ gradient. The Ki/Ke ratio is also dependent on Na+/K+ pump activity which, exchanging intracellular Na+ with extracellular K+, determines intracellular K+ retention and therefore its concentration gradient between intra and extracellular volume. In the uremic patient the retention of nitrogenous catabolites causes the slowing- down in ATP production in Krebs' cycle because of prevalent use of this low -efficiency energetic substrate; ATP supply to Na+/K+ pump, which is ATP-asi- dependent, is reduced and consequently so is pump activity. Thanks to nitrogenous catabolite removal, dialysis recovers the use of other major efficiency energetic substrates, such as carbohydrates and lipids, in Krebs' cycle with an increase of ATP production rate and pump activity. This hypothesis could explain the REMP reduction in end-stage uremia and its correction with dialysis.

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.

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.

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.

Transport of water and solutes in uremic patients with chronic hepatic disease in CAPD.

Ten patients with chronic hepatic disease (CHD) were compared with 34 non-CHD (N) pts. All patients underwent a peritoneal equilibration test; the asymptotic curves for small solutes transport were transformed into straight lines; protein transport was also expressed as a straight line; the slopes of these linear functions were used as index of solute transfer. CHD patients showed increased UF and transport of all solutes. The well-known relationships between UF and glucose absorption and between UF and dialysate sodium concentration were observed in N, but not in CHD patients. In patients without hepatic disease there was also a relationship between UF and the glucose transport slope, which was not observed in CHD pts. These results are probably due to the influence of hepatic lymph production plus increased lymphatic removal, observed in non uremic patients affected by cirrhosis, on the mechanisms of water and solute transport in CAPD. CHD patients can be managed either with CAPD or with short frequent exchanges. Ascites production can be evaluated by the difference between the observed UF in a patient with CHD and the expected UF in N patients.

Electrolyte modelling in haemodialysis--potassium.

Cardiovascular tolerance to haemodialysis is reduced by the appearance of cardiac arrhythmias whose onset is partly caused by an intradialytic increase in cell membrane polarisation. This is due to the current method of dialytic potassium removal based on the use of dialysis baths with a fixed potassium content (constant KD), which leads to a dialytic transmembrane concentration gradient that decreases during the course of dialysis. By varying the potassium concentration in the bath (variable KD) during dialysis, it is possible to obtain a constant dialytic transmembrane concentration gradient. For this study, we selected 36 haemodialysis patients attending 17 dialysis centres in whom Holter monitoring revealed the presence of premature ventricular complexes (PVCs) that increased in number during dialysis. In order to compare the arrhythmogenic effect of the treatments, the patients were randomised to undergo dialysis with a constant or variable potassium concentration according to a cross-over design. The main variable, ln(PVC/h + 1)post-ln(PVC/h + 1)pre = patient effect+direct treatment effect+carry-over effect, was statistically analysed using the analysis of variance. The results show that dialysis carried out using variable potassium concentrations significantly reduced the arrhythmogenic effect of standard dialysis.

Acute renal failure after rifampicin: a case report and survey of the literature.

A new case of acute renal failure after rifampicin is presented, together with a review of the 36 similar cases published up to date in the literature. Evidence is provided that irregularities in drug intake, either as true intermittent treatment or as discontinuation of continuous therapy, play an important role in the pathogenesis of such reactions. Renal failure appeared after a rather long uneventful interval from the beginning of rifampicin therapy, ranging from 1 month to more than 1 year. Its clinical course was favourable in all but one case; the histological picture was mainly of tubulo-interstitial type. The controversial immunological data reported in the literature are reviewed; an increase of histamine release by rat mast cells has been found in presence of rifampicin plus the serum of our patient: the implications of this finding are discussed, suggesting a possible immunological factor in the pathogenesis of acute renal failure after rifampicin.

Prospective, randomised, multicentre trial of effect of protein restriction on progression of chronic renal insufficiency. Northern Italian Cooperative Study Group.

A multicentre, prospective trial was organised to clarify the role of protein restriction in the progression of chronic renal insufficiency (CRI). 456 adult patients were assigned either a low-protein diet (0.6 g/kg body weight daily; n = 226) or a "normal" controlled-protein diet (1.0 g/kg daily; n = 230) and were stratified into three groups (A-C) with increasing baseline plasma creatinine concentrations. Each patient was followed up for 2 years or until an endpoint (a doubling of the baseline plasma creatinine or a need for dialysis) was reached. The difference between the diet groups in cumulative renal survival defined by these endpoints (27 low-protein, 42 controlled-protein) was of borderline significance (p less than 0.06). The difference in renal survival between the low-protein and controlled-protein diet groups was of borderline significance in group A (0 vs 4 endpoints), significant in group B (10 vs 21 endpoints; p less than 0.025), and not significant in group C. There were no differences among the diet groups or subgroups in mean plasma creatinine concentrations, creatinine clearance, the slope of the plasma creatinine reciprocal, or mean blood pressures. Compliance was good in the controlled-protein group but poor for the low-protein diet: the difference in protein intake between the groups was substantially less than that required by the protocol. However, there was no correlation between the progression of renal failure and protein catabolic rate. These findings offer little, if any, support to the hypothesis that protein restriction retards CRI progression: careful medical care and a "normal" controlled protein intake also allow very slow progression of CRI.

Ventricular arrhythmias and four-year mortality in haemodialysis patients. Gruppo Emodialisi e Patologie Cardiovascolari.

127 randomly selected patients on haemodialysis showed a high prevalence of ventricular arrhythmias, the frequency of which rose significantly during and after dialysis. These patients have now been followed up for 4 years. Only age and ischaemic heart disease correlated independently with mortality. Although ventricular arrhythmias are often associated with cardiac disease in patients on chronic haemodialysis, they do not seem to predict overall mortality.

Hypertension as a factor in chronic renal insufficiency progression in polycystic kidney disease. The Northern Italian Cooperative Study Group.

The aim of this study was to evaluate the role of blood pressure in the progression of chronic renal failure (CRF) in polycystic kidney disease, by analysing the behaviour of 74 affected patients, out of 456 CRF patients with various underlying nephropathies enrolled in a multicentre, formal prospective trial aimed at clarifying the role of protein restriction in retarding CRF progression. Because no difference was found between the patients on a low protein and those on a controlled protein diet, an inductive analysis was made by separating all of the patients into fast progressive or slowly progressive CRF groups. Hypertensive patients were defined as those with a mean resting blood pressure of more than 107 mmHg; of the 62 polycystic patients who completed the study or who reached an end point, 41 patients were hypertensive and 21 normotensive (10 of whom were pharmacologically controlled). The results of the stratified analysis, taking into account the degree of renal function deterioration and the underlying disease, showed a significant relationship between hypertension and CRF progression only in patients with polycystic kidney disease.

Hypertension and chronic renal insufficiency: the experience of the Northern Italian Cooperative Study Group.

There is general agreement that hypertension is a prognostic index of the progression of chronic renal insufficiency (CRI), although it remains to be clarified whether this is related to the hypertension per se, or to the underlying disease and the level of CRI. In an attempt to clarify this important point, an inductive analysis was made of the behavior of blood pressure values and their relationship to the progression of CRI in 456 patients (pts) who participated in a multicenter prospective formal randomized trial, designed to compare the effects of a restricted and a controlled protein diet on CRI progression. An analysis was also made (on the population as a whole and by separating the pts into fast progressive and slowly progressive groups) of the type and frequency of the antihypertensive drugs used, the number and type of drugs used in association, and their possible relationship to the progression of CRI. Of the 456 enrolled pts, 406 (89%) were defined as hypertensive at entry (mean blood pressure > 107 mm Hg); 324 out of the 380 pts (85.3%) who completed the 24-month follow-up or reached an end point were treated with antihypertensive drugs. There was a significant difference at entry between the supine blood pressure values of the pts with fast progressive CRI (182 pts), and those of the pts with slowly progressive CRI (198 pts). During the follow-up period, no significant differences were observed between the two groups. There was no difference in the blood pressure levels reached with the different drugs used.(ABSTRACT TRUNCATED AT 250 WORDS)

Factors affecting chronic renal failure progression: results from a multicentre trial. The Northern Italian Cooperative Study Group.

In order to evaluate the prognostic factors concerning the rate of progressive deterioration of renal function, we made an inductive analysis of the behaviour of 456 patients in a multicentre, formal prospective trial aimed at clarifying the possible role of protein restriction in retarding the progression of chronic renal insufficiency (CRI). The main clinical and laboratory findings in patients whose plasma creatinine (PCr) levels doubled in comparison with baseline randomization values or who needed dialysis within 24 months after onset of the study were compared with those of the other patients. In addition, independently of the assigned diet, we tested the main variables that might affect CRI progression (sex, systolic and diastolic blood pressure, change in body weight, hematocrit, calcium-phosphate product, proteinuria, protein catabolic rate, total cholesterol and triglycerides). We used multiple regression analyses and also plotted the mean values of these parameters in each patient against an estimate of the deterioration of chronic renal failure based on the difference between the final and the initial reciprocal of the PCr and the creatinine clearance (CCr) levels. A descriptive analysis of the behaviour of PCr in the three CRI groups and in the four underlying diseases groups was made. PCr levels at entry, underlying disease and proteinuria were prognostic factors for CRI progression. The increase in PCr was 0.0102 mg/dl/month in patients with nephrosclerosis, 0.0203 mg/dl/month in interstitial nephropathy, 0.0360 mg/dl/month in glomerulonephritis and 0.0704 mg/dl/month in polycystic kidney disease.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of different membranes and dialysis technologies on patient treatment tolerance and nutritional parameters. The Italian Cooperative Dialysis Study Group.

There is increasing evidence that the biochemical and cellular phenomena induced by blood/ membrane/dialysate interactions contribute to dialysis-related intradialytic and long-term complications. However, there is a lack of large, prospective, randomized trials comparing biocompatible and bioincompatible membranes, and convective and diffusive treatment modalities. The primary aim of this prospective, randomized trial was to evaluate whether the use of polysulfone membrane with bicarbonate dialysate offers any advantage (in terms of treatment tolerance, nutritional parameters and pre-treatment beta-microglobulin levels) over a traditional membrane (Cuprophan). A secondary aim was to assess whether the use of more sophisticated methods consisting of a biocompatible synthetic membrane with different hydraulic permeability at different ultrafiltration rate (high-flux hemodialysis and hemodiafiltration) offers any further advantages. Seventy-one Centers were involved and stratified according to the availability of only the first two or all four of the following techniques: Cuprophan hemodialysis (Cu-HD), low-flux polysulfone hemodialysis (LfPS-HD), high-flux polysulfone high-flux hemodialysis (HfPS-HD), and high-flux polysulfone hemodiafiltration (HfPS-HDF). The 380 eligible patients were randomized to one of the two or four treatments (132 to Cu-HD, 147 to LfPS-HD, 51 to HfPS-HD and 50 to HfPS-HDF). The follow-up was 24 months. No statistical difference was observed in the algebraic sum of the end points between bicarbonate dialysis with Cuprophan or with low-flux polysulfone, or among the four dialysis methods under evaluation. There was a significant decrease in pre-dialysis plasma beta 2-microglobulin levels in high-flux dialysis of 9.04 +/- 10.46 mg/liter (23%) and in hemodiafiltration of 6.35 +/- 12.28 mg/liter (16%), both using high-flux polysulfone membrane in comparison with Cuprophan and low-flux polysulfone membranes (P = 0.032). The significant decrease in pre-dialysis plasma beta 2-microglobulin levels could have a clinical impact when one considers that beta 2-microglobulin accumulation and amyloidosis are important long-term dialysis-related complications.

Proteinuria and blood pressure as causal components of progression to end-stage renal failure. Northern Italian Cooperative Study Group.

AIMS: To identify the prognostic factors possibly related to end-stage renal failure development. SUBJECTS AND METHODS: The prognostic factors affecting chronic renal failure progression were analysed in 456 patients who had participated in a formal, multicentre, prospective randomized trial aimed at verifying the role of protein restriction in slowing down or halting the progression of chronic renal failure. The 24-month follow-up foreseen by the protocol was completed by 311 patients and 69 reached an end-point. An inductive analysis on patient survival was made by using the Cox proportional hazard regression model, using a stepwise procedure in order to select only those factors which are significantly associated with survival. For each individual risk factor, a univariate descriptive analysis of survival was performed using the Kaplan-Meier technique. RESULTS: Underlying nephropathy, baseline plasma creatinine, proteinuria, and plasma calcium were all shown to be related to end-stage renal failure onset. Hypertensive patients (mean blood pressure > 107 mmHg) had a worst cumulative renal survival but the degree of proteinuria was even more important as a prognostic factor of renal death than hypertension. The cumulative renal survival of patients whose proteinuria decreased during the trial follow-up was better than those of patients without changes. However, the interaction between baseline lying mean blood pressure and proteinuria was not significant. CONCLUSIONS: Only primary renal disease and proteinuria were related to renal survival, being baseline plasma creatinine confounding factor. By blocking the possible causal role of proteinuria and hypertension, end-stage renal failure could be prevented in a significant percentage of patients.

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.