Renal replacement therapy in acute renal failure: which index is best for dialysis dose quantification?

BACKGROUND: The "delivered dose" of dialysis may significantly affect the outcome of acute renal failure (ARF) patients requiring dialysis. Our study aimed to elucidate which dose quantification method offers an appropriate parameter to compare different treatments in ARF patients. METHODS: Six sustained low-efficiency daily dialysis (SLEDD), and 7 continuous venovenous hemofiltration (CVVH) patients with a prescribed Kt/V of 1.0 were studied during a single treatment. CVVH was studied over the first 24 hours after initiation. SLEDD was performed for 6-12 h. Solute clearance (K) was determined by direct dialysate quantification (DDQ). The single-pool Kt/V (spKt/V), equilibrated Kt/V (eqKt/V), equivalent renal urea clearance (EKRc), and solute removal index (SRI) were calculated. RESULTS: There were no significant differences at enrollment between the SLEDD and the CVVH groups in any patient characteristics except for the serum creatinine levels. The prescribed Kt/V of both groups was similar (SLEDD, 0.9+/-0.22; CVVH, 1.10+/-0.12, p=NS). The EKRc, which is used to verify kinetic equivalence among patients treated with differing renal replacement therapies (RRT), was higher in CVVH (15.7 in SLEDD; 27.4 in CVVH, p<0.0001), despite the fact that there was no difference between the delivered spKt/V for the SLEDD (1.05+/-0.40) and the CVVH (1.10+/-0.11) groups. The values for SRIurea (0.61 in SLEDD; 1.04 in CVVH, p=0.001), SRIcreatinine (0.55 in SLED; 1.02 in CVVH, p<0.0001), and SRIphosphate (1.81 in SLED; 3.60 in CVVH, p=0.03) were higher in CVVH. The EKRc is calculated assuming a steady state, which is an incorrect assumption in ARF patients with hypercatabolism. CONCLUSION: The SRI calculated using direct dialysate effluent quantification appears to be more reliable as an index of the dialysis dose compared to other methods in ARF patients. However, the use of the dialysate-side SRI is limited by the difficulty of dialysate effluent collection.

Effect of cyclosporine, mycophenolate mofetil, and their combination with steroids on apoptosis in a human cultured monocytic U937 cell line.

Transplant patient plasma produces an increased rate of mononuclear cell apoptosis despite a normal serum creatinine value. Immunosuppressive medications may be one factor that causes an altered apoptotic pattern. We evaluated the in vitro effects of various doses of cyclosporine, mycophenolate mofetil, and steroids on apoptosis of a cultured human monocytic U937 cell line, using estimates by fluorescence microscopy and annexin V assays. Increasing cyclosporine concentrations (100 to 800 ng/mL) progressively increased apoptosis rates (16% to 32%). The combination of steroid (0.01 microg/mL) and cyclosporine increased the apoptosis rate to 45%. Mycophenolate mofetil alone (0.3 microg/mL) led to an apoptosis rate of 34%. Therapeutic levels of mycophenolate mofetil from 3 to 7 microg/mL led to apoptosis rates from 56% to 67%. The combination of cyclosporine, steroid, and mycophenolate mofetil increased the rate of apoptosis to 95%. Immunosuppressive therapy may contribute to the high rate of apoptosis observed among mononuclear cells of transplanted patients. This effect may alter patient susceptibility to infections and contribute to a unique mechanism of immunosuppression.

Sequential convective therapies (SCT): a prospective study on feasibility, safety, adequacy and tolerance of on-line hemofiltration and hemodiafiltration in sequence.

Sequential dialysis techniques (i.e pure ultrafiltration followed by dialysis) have been used in the past, due to their capability to remove large volumes of fluids without inducing hemodynamic instability. The disadvantages of inadequate efficiency and lack of technology lead to the decline of such methods. Hemofiltration (HF) and hemodiafiltration (HDF) are recently being utilized in a greater proportion thanks to on-line fluid preparation systems. Each process (HF and HDF) has its own benefits in the removal of small, medium and high-molecular weight substances and in hemodynamic stability. Sequential convective therapies (SCT) such as hemofiltration-hemodiafiltration in sequence (HF-HDF) may combine the benefits and eliminate the disadvantages of each method and should be studied in order to explore their potential application in modern dialysis. Furthermore they can be easily applied nowadays, due to the development of new sophisticated dialysis machines. In order to evaluate the feasibility, safety, efficiency and tolerance of different SCT methods we studied 3 schedules: SCT1: 1h pre-dilution HF followed by 3h of post-dilution HDF (in the HF mode we lost 25% of the total fluid that had to be removed). SCT2: 1h pre-dilution HF followed by 3h of post-dilution HDF (in the HF mode we lost 50% of the total fluid that had to be removed). SCT3: 2h pre-dilution HF followed by 2h of post-dilution HDF (in the HF mode we lost 50% of the total fluid that had to be removed). We studied 6 chronic hemodialysis patients using the same machine (AK200 ULTRA), with on-line fluid preparation system and the same type of dialyzer (Polyflux 210). SCT schedules were compared to on-line HF, on-line HDF and high flux dialysis performed with the same dialyzers. The treatments resulted safe, easy, feasible and well tolerated with an improved hemodynamic response to high volume convective therapies. Adequacy of treatment was satisfactory in all SCT schedules while middle molecular weight solute clearance and removal resulted higher in treatments with higher convective component. SCT might represent an interesting option for the future especially in patients with hemodynamic instability and requirements for interventions during treatment.

[Rationale for the use of extracorporeal treatments for sepsis].

Sepsis is the leading cause of disability and mortality among critical patients; moreover, it causes high economic expenditures. Although very much is known about the pathophysiology of this condition and its mediators despite great investments directed to its control, mortality rates remain high. Recent treatment manuals emphasize the value of early goal-oriented therapy and also point to the high efficacy of activated protein C. Extracorporeal blood clearance may potentially become a new approach to treating this condition. There are reports on its positive clinical results that are likely associated with the effective removal of septic mediators. Human and animal studies, few and rather alike as they are, have yielded promising results. It is evident that the use of these procedures is justified; however, their efficiency in sepsis requires large-scale, correctly conducted studies.

First clinical trial for a new CRRT machine: the Prismaflex.

A new CRRT machine has been designed to fulfill the expectations of nephrologists and intensivists operating in the common ground of critical care nephrology. The new equipment is called "Prismaflex" (Gambro-Dasco, Mirandola, Modena) and it is the natural evolution of the Prisma machine that has been utilized worldwide for CRRT in the last decade. We performed a preliminary "alfa trial" to establish usability, flexibility and realiability of the new device. Accuracy was also tested by recording various operational parameters during different intermittent and continuous renal replacement modalities. Forty-one runs were conducted on 13 patients and the difference between delivered and prescribed parameters was always lower than 2%. We concluded that the new Prismaflex is a well designed new machine for CRRT and can be safely and effectively utilized in the critical care nephrology setting.

Pulse high volume hemofiltration.

The sepsis syndrome is the most common cause of acute renal failure and multiple organ dysfunction in critically ill subjects and continues to have an alarmingly high mortality. Normal immune homeostasis is interrupted by a complex storm of inflammatory mediators responsible for the deleterious effects. Extracorporeal blood purification techniques can confer benefits in sepsis by proven non-specific removal of these mediators (pro- or anti-inflammatory), and provide a logical and adequate approach to treat this syndrome. High volume hemofiltration (HVHF) has had the most dramatic effect conferring benefits in hemodynamics, reduction in vasopressor doses and improvement in survival. "Pulse HVHF" is the latest approach which may offer the most efficient results: a daily schedule of 6-8 hours followed by standard CVVH. This paper describes the rationale and potential of this technique. Reliability and tolerance of this technique and biological effects are described.

Blood lactate determined by a portable device in critically ill patients.

Patients with tissue perfusion deficit usually have lactic acidosis or hyperlactacidemia and blood lactate level has been used to diagnose this condition and to monitor the disease progression. We conducted a study to examine the diagnostic accuracy of capillary and arterial lactate (C LAC and strip A LAC) obtained by using a portable lactate analyzer (Accusport) compared with the standard method (A LAC) in this condition. Forty eight patients were included in the study. Strong correlation between C LAC and A LAC as well as strip A LAC and A LAC were demonstrated (r = 0.89 and 0.98 respectively, p <0.05). When determining agreement between C LAC and strip A LAC with the standard method, all but 2 of C LAC - A LAC differences and 2 of strip A LAC - A LAC differences were within the agreement limits (mean +/- 2SD). We conclude that capillary and arterial lactate determined by the tested device, when used and interpreted cautiously, can substitute arterial lactate in the diagnosis of hyperlactacidemia and monitoring the effectiveness of therapy.

Inflammation and subclinical infection in chronic kidney disease: a molecular approach.

Inflammation and infection seem to be important causes of morbidity and mortality in chronic kidney disease (CKD) patients; subclinical infections have been proposed as an important cause of inflammatory syndrome, but to date this hypothesis remains speculative. We developed a method for the molecular detection of the presence of bacterial DNA in a population of CKD patients in order to correlate the molecular data with the degree and level of inflammation and to evaluate its usefulness in the diagnosis of subclinical infection. The study was divided into two phases: (1) a population of 81 CKD patients was screened for the prevalence and level of inflammation and the presence of possible infection, and (2) a subgroup of 38 patients, without evident clinical causes of inflammation, underwent complete molecular evaluation for subclinical infection using bacterial DNA primers for sequencing. Additionally, complete analysis was carried out in the blood and dialysate compartments of the hemodialyzers used. The general population showed a certain degree of subclinical inflammation and no difference was found between patients with and without evident causes of inflammation. Hemoculture-negative patients were positive for the presence of bacterial DNA when molecular methods were used. We found a correlation trend between the presence of bacterial DNA and the increase in hs-CRP, IL-6 and oxidative stress (advanced oxidation protein product) levels and a reduction in the mean fluorescence intensity for HLA-DR. Hemodialyzer membranes seem to have properties that stick to bacteria/bacterial DNA and work as concentrators. In fact, patients with negative bacterial DNA in the circulating blood displayed positivity in the blood compartment of the dialyzer. The dialysate was negative for bacterial DNA but the dialysate compartment of the hemodialyzers used was positive in a high percentage. Moreover our data suggest that bacterial DNA can traverse hemodialysis membranes. Molecular methods have been found to be far more sensitive than standard methods in detecting subclinical infection. The presence of bacterial DNA seems to influence the variation in some parameters of inflammation and immunity. Apart from the limitations and pitfalls, the molecular method could be useful to screen for subclinical infection and diagnose subclinical sepsis when the hemoculture is negative. However, the identification of the microorganism implicated must be done with species-specific primers.

Continuous renal replacement technology: from adaptive devices to flexible multipurpose machines.

OBJECTIVE: To review the evolution of technologies in the development of renal replacement therapies. DATA SOURCES: Articles and published reviews on renal replacement therapies. SUMMARY OF REVIEW: Continuous arterio-venous haemofiltration (CAVH) was the first continuous renal replacement technique capable of overcoming the traditional haemodialysis-related side effects, making possible the treatment of critically ill patients safely and with less physiological instability. The evolution of technology and the progress experienced in intensive care units (ICUs) has made it possible to start renal replacement therapy programs in the absence of a chronic dialysis facility or a trained nephrological team. Initial limitations and draw-backs of CAVH, stimulated the ICU staff to explore new avenues for better therapy. Extracorporeal therapies are today a routine experience in the ICUs: continuous renal replacement therapies are a broadly accepted treatment for acute renal failure. Furthermore, alternative indications for extracorporeal blood circulation (e.g. sepsis, liver failure, congestive heart failure, drug intoxications, hyperthermia, immuno-mediated syndromes) are becoming more and more popular. The ideal machine has yet to be completed, but progress has occurred and has opened a new era for critical care nephrology and the further expansion of blood purification technology in the ICU. CONCLUSIONS: Technical advances in renal replacement therapies have increased their functionality (i.e. used in hepatic failure, sepsis, cardiac failure and immuno-mediated syndromes), are easier to operate and have less side-effects compared with their standard extracorporeal counterparts. Further improvements may see them become a routine part in the management of the critically ill patient.

Blood lactate determined by a portable device in critically ill patients.

Patients with tissue perfusion deficit usually have lactic acidosis or hyperlactacidemia and blood lactate level has been used to diagnose this condition and to monitor the disease progression. We conducted a study to examine the diagnostic accuracy of capillary and arterial lactate (C LAC and strip A LAC) obtained by using a portable lactate analyzer (Accusport) compared with the standard method (A LAC) in this condition. Forty eight patients were included in the study. Strong correlation between C LAC and A LAC as well as strip A LAC and A LAC were demonstrated (r = 0.89 and 0.98 respectively, p <0.05). When determining agreement between C LAC and strip A LAC with the standard method, all but 2 of C LAC - A LAC differences and 2 of strip A LAC - A LAC differences were within the agreement limits (mean +/- 2SD). We conclude that capillary and arterial lactate determined by the tested device, when used and interpreted cautiously, can substitute arterial lactate in the diagnosis of hyperlactacidemia and monitoring the effectiveness of therapy.