Plasma acid-base changes in chronic renal failure: a Stewart analysis.

The bicarbonate centered approach to acid-base physiology involves complex explanations for the metabolic acidosis associated with chronic renal failure. We used the alternate Stewart approach to acid-base physiology to quantify the acid-base chemistry of patients with chronic renal failure. We examined the plasma and urine chemistry of 19 patients with chronic renal failure who were predialysis and 20 healthy volunteers. We compared the plasma strong-ion-difference due to sodium,potassium,and chloride ions as well as the weak acids albumin and phosphate. We used a simplified Fencl-Stewart approach to quantify the effects of sodium-chloride, albumin, and unmeasured ions on base-excess. The chronic renal failure group had a greater metabolic acidosis, with a base-excess that differed from the healthy group by a mean of -2.7 mmol/L, p = 0.04. This was associated with a strong ion acidosis due to both increased chloride and decreased sodium. The anion gap, strong-ion-gap, and base-excess effect of unmeasured ions were similar in both groups suggesting that unmeasured ions had only a minor role in the acid-base status in this group of patients.

Practice pattern and treatment options for kidney patients in a single North Italian nephrology center.

The experience and the current practice of a single center located in northern Italy is reported. The center of Vicenza is a self-standing nephrologic unit serving a population of about 300,000 individuals. The overall province counts approximately 800,000 individuals and some of them are referred to our center from peripheral hospitals for renal transplantation and/or particular pathologic conditions. The center offers an integrated approach to the treatment of uremia including hemodialysis (HD), peritoneal dialysis (PD), and renal transplantation. In HD and PD, the most peculiar aspect is the treatment personalization that leads to numerous types of applied therapies and technologies. The policy of the center is based on the belief that the nephrology team has a substantial influence on the outcomes of dialysis patients. A large number of treatment options are available. Special care is placed on the delivery of an adequate amount of dialysis, but the fractional clearance of urea in relation to volume (Kt/V) is seen as a prerequisite and other factors are considered important. Reduction in mortality and morbidity is largely dependent on beginning therapy early in the course of renal treatment. The attainment of appropriate hemoglobin concentrations, good nutrition, good control of calcium and phosphorus metabolism, lipids, and blood pressure, is considered of great importance. Beyond all these factors the time spent by the physician with the patient is considered one of the major factors influencing quality of care. The particularly low mortality of the center (6%/yr) may also be ascribed to a lower incidence of diabetes and other comorbidities.

Preliminary technical and clinical evaluation of a new hollow fiber dialyzer with a 5 microns thick cuprophan membrane.

In vitro and in vivo studies were performed on 10 dialyzers with 5 microns thick cuprophan membrane to evaluate hydraulic properties and permeability to solutes. Inlet and outlet pressures of the filter were measured at different blood flows to assess the resistance of the device and the end-to-end pressure drop. Hysolated ultrafiltration was performed to evaluate the spontaneous filtration at increasing blood flows, the ultrafiltration rate at different transmembrane pressures and, finally, the sieving coefficients for solutes. Standard hemodialysis was also performed to study the clearances throughout a 4-h session. During hysolated ultrafiltration the UF rate was increased up to 37 ml/min showing a very high hydraulic permeability of the membrane. The spontaneous filtration rates related to blood flow were quite low. Since the end-to-end pressure drop in the filter was also relatively low at high blood flow we may conclude that the geometry of the device is able to dissociate the influence of blood flow on the hydrostatic pressure inside the filter. This results in a easy modulation of the membrane permeability to water. Sievings were surprisingly high and clearances were stable along the dialysis session (BUN = 196 ml/min, creatinine = 161 ml/min and phosphate = 163 ml/min).

Pathophysiology of ultrafiltration in peritoneal dialysis.

Pathophysiology of peritoneal ultrafiltration is analyzed in the present study. Peritoneal equilibration test is the easiest procedure to study in detail the possible causes of failure to control the ultrafiltration rate in patients undergoing peritoneal dialysis. Membrane failure, reduction in peritoneal blood flow, excessive lymphatic reabsorption catheter malposition, and fluid sequestration are the most common causes of ultrafiltration loss. Pharmacologic manipulation of peritoneal membrane, correction of mechanical inconvenients, reduction in peritonitis rate and in the level of immunostimulation of the mesothelial macrophages, together with a careful policy in terms of glucose concentration in the dialysate and dwell times may contribute not only to treat different forms of ultrafiltration loss but also to prevent their incidence.

A multicenter, selection-adjusted comparison of patient and technique survivals on CAPD and hemodialysis.

Four hundred and eighty CAPD and 373 HD patients started regular dialysis treatment between 1981 and 1987 in 6 dialysis centers. The CAPD patients were 6 years older, on average, than the HD patients and had more complicating conditions (43.3% with 3 or more coexisting risk factors versus 28.9% with coexisting complications). The 7-year patient survival rate was not significantly different. Cox's proportional hazards regression showed that age, cardiovascular disease, cerebrovascular disease, peripheral vascular disease, diabetes, malignancy and multisystem disease had significant adverse effects on patient survival. After correcting for the influence of these factors, no significant differences in patient survival were seen. However, after 53.5 years of age, the increase in the risk of death was significantly higher in HD than in CAPD patients. Technique survival was significantly different in the 6 centers and was better for HD than for CAPD. There was no statistically significant difference between CAPD and HD technique survival when peritonitis was eliminated as a cause of failure. Based on this 7 year analysis, CAPD would appear to be an excellent alternative to HD.

Oxalate removal by differing dialysis techniques.

Secondary hyperoxalemia is a common feature in patients with chronic renal failure, but oxalate removal is not adequately accomplished by regular dialysis treatment. Oxalate removal in two groups of patients, 11 on continuous ambulatory peritoneal dialysis (CAPD) and 12 on hemodialysis (HD), was investigated. HD patients were studied during a regular bicarbonate dialysis and during hemodiafiltration (HDF) with a high convective component (UF = 66 mL/min) and AN69 filter (Hospal Filtral 12, 1.2 m2, Hospal Industrie, Meyzieu, France). All HD and HDF spent dialysate and all 24 hr CAPD effluents were collected; oxalate concentration was measured by high performance liquid chromatography (HPLC) using an ion exchange column. Both oxalate flux and total extraction were statistically higher during HDF treatments (HDF = 1.87 +/- 0.77 mg/min and 335.9 +/- 131.5 mg/session, respectively; HD = 0.99 +/- 0.74 mg/min, 226 +/- 153 mg/session, respectively; p < 0.02). The positive interaction of convective and diffusive fluxes probably played a major role in oxalate removal during treatment with a high convective component; solute-membrane interactions can occur by using either cellulosic or synthetic fibers. In CAPD patients, oxalate removal (76.42 +/- 50.85 mg/day) was lower than in patients on either HD or HDF, although weekly oxalate extraction was statistically no different between CAPD (535.46 +/- 356 mg/week) and HD (677.72 +/- 460.82 mg/week). It was concluded that HDF is more effective than HD or CAPD in oxalate removal. Long-term studies are needed to demonstrate whether these kinetic findings have clinical relevance.

Double pass dialysis: a new method of renal replacement in patients with malfunctioning vascular access.

Several patients undergoing chronic renal replacement therapy present problems related to their vascular access. Low blood flows and high rates of recirculation are common in such patients in which, for this reason, it becomes difficult to apply highly efficient techniques or techniques where diffusion and convection are combined as in hemodiafiltration. In these patients we studied the possibility of partially recirculating the blood in the extracorporeal circuit in order to increase the flow rate per single hollow fiber; we defined our system "double pass dialysis". We evaluated the system's efficiency in 12 patients during 24 dialysis sessions: 12 high flux dialysis sessions (without reinfusion) and 12 hemodiafiltration sessions (9 liters reinfusion). Different surfaces of polyacrylonitrile dialyzers were utilized (1.3-1.7-2.1 sqm) at 250 and 350 ml/min of blood flow with or without 100 ml/min of recirculation. During each dialysis session blood and dialysate samples were taken in order to calculate BUN, Creatinine, Phosphate and Inuline clearances from both the blood and dialysate side. The clearances of low molecular weight solutes were not really influenced by the artificial increase of the blood flow, but on the other hand, the clearances of higher molecular weight solutes increased from 10 to 30% during both high flux dialysis and hemodiafiltration with recirculation. This increase was evident mostly in hemodiafiltration suggesting that the cleaning effect on the membrane has a positive impact on the permeability. The good clinical results obtained with the double pass dialysis show that the system is safe and reliable and may become a valid support in critical situations in order to reach adequate dialysis treatment.

Buffer kinetics in biofiltration.

A condition of metabolic alkalosis has been generally observed in patients undergoing regular biofiltration (BF). The aim of this study was to assess buffer kinetics during a dialysis session in five patients regularly treated by BF for 10 months (dialyzer Biospal 3000S, Qb 301; Qd 545; UF 36.76 ml/min; dialysate CH3 COO 38 mEq/L; replacement fluid 1000 ml/h with HCO3 100 mEq/L solution). As usually happens using dialyzers with high surface area and permeability, large HCO3 losses (756 +/- 112 mEq) and CH3COO uptakes (677 +/- 152 mEq) were observed. Acetate plasma levels rose to 10.4 mEq/L, a value potentially dangerous to the cardiovascular system. The dialytic buffer gain (acetate uptake + HCO3 administered - HCO3 loss) was high (230 +/- 137 mEq/dialysis) and excessive for patients' needs. It is therefore very important to reduce either the acetate concentration in dialysate or the amount of reinfused bicarbonate. In view of the plasma acetate levels it is preferable to use a dialysis solution containing less acetate.

Solute and water transport during continuous arteriovenous hemofiltration (CAVH).

The transport mechanisms governing solvent and solute removal during CAVH were elucidated on the basis of in vitro and in vivo observations. Using a typical hemofilter (Diafilter D-20, AMICON), filtration rate rose with inlet blood flow rate until an asymptote was reached at blood flows of approximately 150 ml/min. The onset of the asymptote coincided with transition from a regime controlled by oncotic pressure (filtration pressure equilibrium), to one governed by simple Darcy's law filtration behaviour. Subsequent measurements showed that under clinical conditions, CAVH is generally in the pre-asymptotic regime and operates at filtration pressure equilibrium. These observations offer the theoretical bases for a new design for CAVH hemofilters. As a possible corollary, middle-molecule sieving coefficients were found to be stable with time during CAVH in vivo, whereas in chronic mechanical hemofiltration they declined significantly during clinical treatment. The sieving coefficients, however, were lower in mechanical hemofiltration from the beginning of the session. These observations suggest that the measured sieving coefficient for a membrane is not necessarily a constant directly and solely related to the membrane standard reflection coefficient for a given solute. Concentration polarization and the ultrafiltration rate per unit of surface area may in fact have a major effect on the final concentration of solutes in the ultrafiltrate.

Technical and clinical evaluation of a new polyamide hollow fiber hemofilter for CAVH.

We carried out an in-vivo and in-vitro evaluation of a new polyamide hollow fiber hemofilter especially designed to operate under conditions of low pressure and low blood flow, such as in continuous arteriovenous hemofiltration (CAVH). The results obtained suggest that this filter is a prototype of a new generation of hemofilters especially designed for CAVH. Its low resistance permits its use even in patients with severe hypotension. The high blood flows achieved at a given pressure reduce the risk of clotting and increase the ultrafiltration rate. When an average ultrafiltration of 20-25 ml/min is achieved in 24 hours CAVH becomes very efficient, and alternative techniques to increase its efficiency are no longer required.

A new blood module for continuous renal replacement therapies.

A new blood module for continuous renal replacement therapies has been utilized to perform CVVH in critically ill patients. The features of the new module named (HP300 and manufactured by Medica srl (Medolla, Modena) are the easy installation and transportability to the bedside, the simple and safe management and the continuous measurement of the pre and post filter pressure with automatic calculation of the end-to-end pressure drop inside the filter. The last feature permits to detect early malfunctions of the filter due to fibers clotting or due to the internal coating of the hollow fibers by plasma proteins. In both cases the efficiency of the treatment can be reduced because of a significant reduction of the ultrafiltration rates or a remarkable decay of the membrane permeability and solute sieving coefficients. In many cases this reduction is only detected when important effects on solute removal have already occurred. In our experience, the new module permitted the substitution of the filters when early malfunctions were detected and maximal treatment efficiency was therefore guaranteed over extended periods of time.

New method of extracorporeal concentration of ascitic fluid as a treatment of refractory ascites.

A new piece of equipment for the treatment of ascites is described. Ascitic fluid is drained by gravity in a unit consisting of an Amicon D-30 ultrafilter and a bag used as transit reservoir placed below the patient. When the bag is full, it is raised to a height sufficient to let the fluid flow back through the filter to the peritoneal cavity. Mainly during this step ultrafiltration of ascitic fluid occurs through the membrane of the filter. Ultrafiltration is enhanced by the negative pressure created in the filtrate compartment due to the height difference between filter unit and filtrate drainage bag placed at the bottom of the machine. Proteins in the ascitic fluid are retained and returned to the abdominal cavity. The machine cycle is automatically repeated as many times as necessary to achieve the scheduled patient weight loss. 17 patients have been treated for a total of 1.94 sessions/patient with reinfusion of the fluid in the abdominal cavity. In all patients a significant reduction of the amount of ascitic fluid and of its rate of formation have been achieved. The treatment was well tolerated and no side effects were observed. After treatment the diuresis and the sodium excretion increased significantly in all patients. The system is safe and reliable for the treatment of refractory ascites without major complications.

Comparison of four different short dialysis techniques.

The goal of shortening dialysis treatment time has stimulated the development of new, highly efficient dialytic strategies. In this study the Authors compared four different short dialysis treatments in terms of efficiency, clinical tolerance, technological investment and costs: 1) Rapid bicarbonate dialysis with 1.5 sq.m. cuprophane membrane; 2) High flux biofiltration with 1.2 sq.m. AN69S hollow fiber membrane; 3) Hemodiafiltration with 1.2-1.9. sq.m. polysulphonic hollow fiber hemodiafilters, and 4) High flux hemodiafiltration with two serial hemodiafilters with AN69s membrane (total 2.4 sq.m.). Hydraulic properties and solute clearances at different blood flows (300-500 ml/min) were tested for each technique. Once the optimal operative level was established three patients were treated with each technique for at least six months. Since BUN clearance averaged 310 ml/min, the treatment duration varied from 120 to 180 min/session with KT/V always higher than 1. The average protein catabolic rate was 0.9 g/kg/24h. Clinical tolerance was generally good, slightly better in treatments with a high convective component. Despite the greater efficiency of treatment No. 4, the technological requirements and costs are such that the others are currently more feasible and acceptable in clinical routine. The study demonstrates that reduction of dialysis treatment time is possible in all centres in a selected population with adequate blood access. Treatment No. 1 can even be performed with standard equipment and cuprophan membranes, while bicarbonate in the dialysate is mandatory. The real limit to shortening treatment time seems to be related to the maximal rate of ultrafiltration achievable in the patient during dialysis.

Acid base correction in bicarbonate CAPD patients.

Bicarbonate has been proposed as buffer in CAPD solutions in recent years instead of lactate and acetate. The present study is designed to evaluate peritoneal bicarbonate kinetics using bicarbonate solutions. Seventy kinetic studies have been performed in 7 patients treated with 2 CAPD solutions containing 35 mmol/l (A) and 27 mmol/l (B) of bicarbonate. The changes in dialysate bicarbonate concentration at different dwell times were correlated with bicarbonate blood levels. Furthermore after 2 hours of dwell time and at subsequent observations, no differences in dialysate bicarbonate concentration were found between A and B solutions at the same bicarbonatemia. Thus a feedback between bicarbonate absorption and bicarbonate blood concentration was observed. If the amount of bicarbonate transferred to the patient is over the metabolic acid production, bicarbonatemia will rise: consequently bicarbonate dialysate absorption will decrease. After a few days, an equilibrium point will be reached. In this condition the bicarbonate absorption is equal to metabolic acid production and, in stable clinical conditions, a stable acid base status will be maintained by the patient. Our studies empirically demonstrated that the equilibrium is reached when a difference of 5 mmols between blood and inlet dialysate bicarbonate concentration is observed. Consequently to achieve 25 mmol/l of bicarbonatemia, the bicarbonate concentration of CAPD solution should be about 30 mmol/l.

TINU syndrome associated with reduced complement levels.

The TINU syndrome (tubulointerstitial nephritis and uveitis) was first described by Dobrin et al. in 1975. Since then, more than 50 cases have been documented each with diverse immunopathogenetic and genetic characteristics. The aim of this report is to describe a case of TINU associated with reduced complement levels. We profile a 48-year-old white female with persistently reduced C4 complement levels during the acute phase of the pathology and with an unaltered immunologic profile. Renal biopsy evidenced a significant lymphocytic interstitial infiltration. Immunohistochemical studies of the interstitium infiltrates was positive for the presence of the T (CD3) markers (CD4 > CD8). Steroid therapy yielded a complete regression of the symptomatology with normalization of the complement levels. We suggest that it is possible to hypothesize that the various immunologic alterations associated with TINU, including the transient reduction complement levels, may be secondary to multiple inflammatory mechanisms which express themselves throughout the pathology.

Effect of dialysate and substitution fluid buffer on buffer flux in hemodiafiltration.

The effect of differing dialysate and substitution fluid buffer types and concentrations on acid-base balance have not been assessed in patients treated with hemodiafiltration for ESRD. To determine bicarbonate, acetate, lactate and total buffer flux, mass balance studies were performed in patients treated with hemodiafiltration using four different combinations of dialysate and substitution fluids. Driving force for bicarbonate flux was assessed in all treatments. Bicarbonate flux depended on bicarbonate driving force and ultrafiltration rate. Bicarbonate flux was negative in all treatment combinations, even when the driving force was positive. Acetate flux was positive in all treatment combinations, but the net magnitude was small. Lactate flux, when lactate containing substitution fluid was used, varied with dialysate buffer employed during treatment. Overall buffer flux depended on the bicarbonate driving force, ultrafiltration rate, and varied with the type of substitution and dialysate buffer employed. The types and concentrations of buffer used in dialysate and substitution fluid have important effects on the acid-base balance of patients treated with hemodiafiltration. The long-term implications of different therapeutical choices in these patients is unknown.