Removal of inflammatory cytokines and endotoxin by veno-venous continuous renal replacement therapy for burned patients with sepsis

OBJECTIVE: To evaluate the effect of veno-venous continuous renal replacement therapy (CRRT) on the plasma levels of endotoxin and cytokines in severely burned patients with sepsis. METHODS: Twenty adult severely burned patients with sepsis were studied. For the diagnosis of sepsis, patients were randomly divided into CRRT (n=10) and Control (n=10). Both groups received conventional therapy after admission. Veno-venous CRRT was administered to 10 patients in the CRRT group whenever patients were determined to be septic. The plasma level of endotoxin, TNF-alpha, IL-1 beta, IL-6 and IL-8 were measured at 0, 1, 2, 6, 12, 36 and 60 h after CRRT initiation, and at 0, 12, 36 and 60 h after the patients were diagnosed as having sepsis in the Control group. MAIN RESULTS: Plasma level of endotoxin and all the cytokines after CRRT initiation were significantly lower than those before the treatment (P<0.01). The serial change of endotoxin, IL-1 beta, IL-6 and IL-8 was significantly lower at 12, 36 and 60 h after treatment compared with Control groups (P<0.01). A significant decrease in plasma TNF-alpha levels was seen at 36 and 60 h after treatment compared with Control groups (P<0.01). CONCLUSION: Plasma endotoxin and cytokines (TNF-alpha, IL-1 beta, IL-6 and IL-8) can be removed effectively with CRRT in severely burned patients with sepsis.     

Ionized serum calcium levels during acute renal failure: intermittent hemodialysis vs. Continuous hemodiafiltration

BACKGROUND: Achieving "adequacy of dialysis" includes the maintenance of normal serum ionized calcium concentrations and is an important therapeutic goal in the treatment of acute renal failure (ARF). It is unknown whether this goal is best achieved with intermittent or continuous renal replacement therapy. METHODS: We compared the effects of continuous veno-venous hemodiafiltration (CVVHDF) and intermittent hemodialysis (IHD) on serum ionized calcium concentrations using daily morning blood tests in 88 consecutive intensive care patients of which half were treated with IHD and half with CRRT. RESULTS: Mean patient age was 54 +/- 14 years for IHD and 60 +/- 14 years for CVVHDF (NS). However, patients who received CVVHDF were significantly more critically ill (mean APACHE II scores: 24.4 +/- 5.1 for IHD vs. 29.2 +/- 5.7 for CVVHDF, p < 0.003). Before treatment, the mean ionized calcium concentration was 1.177 +/- 0.03 mmol/l for IHD and 1.172 +/- 0.04 mmol/l for CVVHDF (NS), with abnormal values in 51.6% of IHD patients and in 68% of CVVHDF patients (NS). During treatment, hypocalcemia was significantly more common among CVVHDF patients (24.5% vs. 14.9%; p < 0.011) while hypercalcemia was more frequent during IHD (36.1% vs. 25.6%; p < 0.019). CONCLUSIONS: Abnormal serum ionized calcium concentrations are frequent in ARF patients before and during renal replacement. Once dialytic therapy is applied, CVVHDF is more likely to lower serum calcium concentrations, while IHD is more likely to induce hypercalcemia. Appreciation of these different biochemical effects may assist clinicians in adjusting dialytic therapy in selected patients.     

Catabolism in critical illness: estimation from urea nitrogen appearance and creatinine production during continuous renal replacement therapy

Thirty-eight intensive care unit (ICU) patients (26 men and 12 women with a mean age of 57.0 +/- 16.6 years) with acute renal failure (ARF) treated by venovenous continuous renal replacement therapy (CRRT) were evaluated while in relatively steady metabolic control. Twenty-seven were undergoing continuous venovenous hemodialysis, nine were undergoing continuous venovenous hemodiafiltration, and two were undergoing continuous venovenous hemofiltration. Periods of analysis varied between 24 and 408 hours (mean duration, 82.7 +/- 70.6 hours; median, 72 hours). Their mean Acute Physiology and Chronic Health Evaluation II (APACHE II) score within 24 hours of admission to the ICU was 21.3 +/- 6.3 and survival rate was 31.6%. Urea nitrogen and creatinine concentrations were determined every 6 to 12 hours in both serum (Cun and Cc, respectively) and effluent (spent dialysate and/or ultrafiltrate). The mean effluent rate was 1,472 +/- 580 mL/h and blood flow rate, 166 +/- 32 mL/min. Urine was collected daily for urea nitrogen and creatinine measurement. Urea nitrogen appearance rate (UnA) and creatinine production rate (Pc), calculated from urea nitrogen (UnMR) and creatinine mass removal (CMR) from both the effluent and the urine, using Garred mass balance equations and the Forbes-Bruining formula, allowed normalized protein catabolic rate (nPCR) and estimates of lean body mass (LBM) to be derived. Creatinine metabolic degradation rate (Dc), estimated by the Mitch formula, was included in the calculation. The lowest body weight recorded during the study period was considered as dry weight (BW). The creatinine index (CI) was also obtained. For each parameter, the results are presented as mean, median, and range values: UnMRe (from effluent), 13.6 +/- 7.2, 12.5, 1.6 to 32.6 mg/min; UnMRu (from urine), 0.13 +/- 0.40, 0, 0 to 2.30 mg/min; UnA, 13.6 +/- 7.0, 12.5, 3.8 to 32.1 mg/min; nPCR, 1.75 +/- 0.82, 1.60, 0.61 to 4.23 g/kg/d; CMRe (from effluent), 942.0 +/- 362.3, 918.0, 211.2 to 1,641.6 mg/d; CMRu (from urine), 44.4 +/- 138.8, 0, 0 to 698.5 mg/d; Dc, 94.6 +/- 49.9, 81.9, 31.0 to 294.1 mg/d; Pc total, 1,067.1 +/- 409.7, 1,053.7, 261.5 to 1,988.2 mg/d; LBM, 38.3 +/- 11.9, 37.9, 15.0 to 65.0 kg; LBM/BW ratio, 49.5% +/- 14.0%, 50.3%, 22.5% to 86.0%; and CI, 13.7 +/- 4.7, 14.2, 4.1 to 25.8 mg/kg/d. When Pc was estimated from the Cockcroft-Gault equations (as Pc'), the mean value for Pc and Pc' was similar (1,067.1 +/- 409.7 v 1,284.9 +/- 484.1 mg/d), but there were relatively large differences for the majority of cases. A positive correlation was observed between UnA and Pc (R = 0.42). Serum albumin and LBM/BW correlated poorly (R = 0.20). Outcome was weakly related to UnA and to nPCR (R = 0.29 and R = 0.31, respectively). Urea nitrogen appearance appears widely variable in critically ill ARF patients. This simple approach can provide useful information for an easy estimate of net protein catabolism in critically ill patients with ARF undergoing CRRT.     

Continuous veno-venous hemodiafiltration in children after cardiac surgery

Objective: Acute renal failure (ARF) is still a frequent complication following extensive cardiac surgery. Renal replacement therapy (RRT) modality preferences to treat critically ill children have shifted from peritoneal dialysis to continuous renal replacement therapy (CRRT), although the experience with the latter is still highly limited in the infants. Methods: We describe our results with continuous veno-venous hemodiafiltration (CVVHDF) in 25 children (15 males, 10 females) who underwent CRRT from 2001 to 2006 and were retrospectively reviewed. Results: We performed continuous veno-venous hemodiafiltration (CVHDF) using PRISMA (Hospal). The mean age at the onset of CRRT was 26 months (ranging from 7 days to 11.2 years) and the mean body weight was 14 kg. The mean duration of RRT was 67 h (8–243 h) with ultrafiltration rate 4.9 ml/(h kg); the mean filter ‘lifetime’ was 31.5 h. Anticoagulation was achieved with non-fractioned heparin infusion (21/25 cases) and enoxaparin (2/16). The mean creatinine concentrations at the beginning, 24, 48 and 72 h were as follows: 171, 100, 65 and 88 μmol/l. Of these 25 treated children, 19 died in the postoperative period (8 during CVVHDF). The mortality rate for the entire group was 76%. The main cause of death was cardiac failure and sepsis with multiorgan dysfunction (MODS). The main complication during CRRT was bleeding, transient hypothermia, thrombocytopenia and filter clotting which occurred in about one-third of the patients. Conclusions: We conclude that CVVHDF may be an alternative method of renal support for critically ill children after cardiac surgery in experienced centers, but a significant number of specific complications should be taken into account.     

Continuous renal replacement therapy and plasma exchange in newborns and infants

The objective of our study was to present our experience in the treatment of small children with continuous renal replacement therapy (CRRT) and plasma exchange (PE). From March 1986 to April 2000, 21 critically ill children (14 newborns and 7 infants) with acute renal failure (ARF) and multiple organ failure were treated with CRRT and PE. In the newborn group, there were 8 males and 6 females, age 15.7 +/- 11.7 days, with body weights of 3,348 +/- 585 g. In the infant group, there were 4 males and 3 females, age 118 +/- 67 days, with body weights 5,186 +/- 734 g. The indications for the beginning of CRRT and/or PE were ARF with anuria and hyperhydration (17 patients), azotemia and anuria (1 patient), hemolytic uremic syndrome (1 patient), and hyperammonemia (2 patients). In all patients, peritoneal dialysis was considered inappropriate. PE and CRRT monitors were used, double lumen 5 Fr and 7 Fr hemodialysis catheters were the vascular access, low dose heparin and prostacyclin were anticoagulants, and lactate or bicarbonate buffered replacement solutions were used predilutionally. Side events were clotting within the extracorporeal circuit, catheter malfunction, serious hypotension (6 patients), and pulmonary edema (1 patient). Ten of 21 patients (47.6%) recovered renal function and 9 of 21 patients (42.9%) survived. Survivors had fewer failing organs (3.6 +/- 0.5) than nonsurvivors (4.8 +/- 0.9) (p = 0.0008). Pump driven CRRT and PE were feasible, efficient, and safe procedures in newborns and infants. Without CRRT, it is uncertain whether any of our patients would have the chance to survive.     

Continuous renal replacement therapy improves renal recovery from acute renal failure

BACKGROUND: Acute renal failure (ARF) occurs in up to 10% of critically ill patients, with significant associated morbidity and mortality. The optimal mode of renal replacement therapy (RRT) remains controversial. This retrospective study compared continuous renal replacement therapy (CRRT) and intermittent hemodialysis (IHD) for RRT in terms of intensive care unit (ICU) and hospital mortality, and renal recovery. METHODS: We reviewed the records of all patients undergoing RRT for the treatment of ARF over a 12-month period. Patients were compared according to mode of RRT, demographics, physiologic characteristics, and outcomes of ICU and hospital mortality and renal recovery using the Chi square, Student's t test, and multiple logistic regression as appropriate. RESULTS: 116 patients with renal insufficiency underwent RRT during the study period. Of these, 93 had ARF. The severity of illness of CRRT patients was similar to that of IHD patients using APACHE II (25.1 vs 23.5, P = 0.37), but they required significantly more intensive nursing (therapeutic intervention scale 47.8 vs 37.6, P = 0.0001). Mortality was associated with lower pH at presentation (P = 0.003) and increasing age (P = 0.03). Renal recovery was significantly more frequent among patients initially treated with CRRT (21/24 vs 5/14, P = 0.0003). Further investigation to define optimal timing, dose, and duration of RRT may be beneficial. CONCLUSIONS: Although further study is needed, this study suggests that renal recovery may be better after CRRT than IHD for ARF. Mortality was not affected significantly by RRT mode.     

Early hemofiltration improves survival in post-cardiotomy patients with acute renal failure.

OBJECTIVE: The application and timing of hemofiltration (continuous veno-venous hemofiltration, CVVH) in patients with acute renal failure (ARF) post cardiac surgery has been called into question because of uncertain short-term outcome. The aim of the present study was to identify how the timing of introduction of hemofiltration affects the morbidity and mortality in patients with ARF after cardiac surgery. METHODS: 1264 consecutive patients who underwent adult cardiac surgical procedures performed between January 2002 and January 2003 were audited. Out of these, case notes of 64 patients who required renal supportive intervention were reviewed. Statistical significance was accepted at a level of P<0.05. RESULTS: Of the 64 (5%) patients, who developed ARF and required CVVH, there were 48 males and 16 females. Mean age was 70+/-6.8 years. The hospital mortality was 43% (12 patients) in Group-I and 22% (8) in Group-II (P<0.05), giving an overall 1.5% mortality associated with ARF. The mean time between the operation and the initiation of CVVH was 2.55+/-2.2 days in Group-I and 0.78+/-0.2 days in Group-II (P<0.001). The mean duration of CVVH was 4.57+/-11.4 days in Group-I and 4.61+/-2.0 days in Group-II (P=NS). Older age (P=0.013), elevated preoperative creatinine (P=0.002), postoperative pulmonary oedema (P=0.01), sepsis (P=0.001), multiple organ failure (P=0.031), hypotension (P=0.031) and preoperative renal failure (P<0.05) were the independent factors influencing the poor postoperative outcome and cardiac instability. CONCLUSION: Early and aggressive use of CVVH is associated with better than expected survival in severe ARF after cardiac operations.     

Continuous renal replacement therapy: does technique influence azotemic control?

BACKGROUND AND OBJECTIVES: Different techniques of continuous renal replacement therapy (CRRT) might have different effects on azotemic control. Accordingly, we tested whether continuous veno-venous hemodiafiltration (CVVHDF) or continuous veno-venous hemofiltration (CVVH) would achieve better control of serum creatinine and plasma urea levels. DESIGN: Retrospective controlled study. SETTING: Two tertiary Intensive Care Units. PATIENTS: Critically ill patients with acute renal failure (ARF) treated with CVVHDF (n = 49) or CVVH (n = 50). Interventions: Retrieval of daily morning urea and creatinine values before and after the initiation of CRRT for up to 2 weeks of treatment. MEASUREMENTS AND RESULTS: Before treatment, serum urea and creatinine concentrations were significantly lower in the CVVH group than in CVVHDF group (urea: 31.0 +/- 15.0 mmol/L for CVVHDF and 24.7 +/- 16.1 mmol/L for CVVH, p = 0.01, creatinine: 547 +/- 308 micromol/L vs. 326 +/- 250 micromol/L, p < 0.0001). These differences were still significant after 48 h of treatment (urea: 20.1 +/- 8.3 mmol/L vs. 14.1 +/- 6.1 mmol/L; p = 0.0003, creatinine: 360 +/- 189pmol/L vs. 215 +/- 118 micromol/L; p < 0.0001). Throughout the duration of therapy, mean urea levels (22.3 +/- 9.0 mmol/L for CVVHDF vs. 16.7 +/- 7.8 mmol/L for CVVH, p < 0.0001) and mean creatinine levels (302 +/- 167 vs. 211 +/- 103 micromol/L, p < 0.0001) were better controlled in the CVVH group. CONCLUSIONS: CRRT strategies based on different techniques might have a significantly different impact on azotemic control.     

Dose of dialysis in acute renal failure

Acute renal failure (ARF) is a cause of significant morbidity and mortality. Despite advances in supportive care, outcomes in ARF have improved little over the past decades. The primary goals in management of patients with ARF are to optimize hemodynamic and volume status, minimize further renal injury, correct metabolic abnormalities, and permit adequate nutrition. Renal replacement therapy (RRT) is often required to achieve these goals while awaiting renal recovery, but the optimal dose of dialysis in patients with ARF is not known. Extrapolation of required dialysis dose from recommendations in chronic dialysis is unlikely to be appropriate because of the lack of a steady state and differences in distribution volume of urea that are intrinsic to ARF. The prescribed dialysis dose in ARF is often low, and actual delivered dose is often even less than prescribed. Delivery of dialysis in ARF is often hampered by the patient's hypercatabolic state, hemodynamic instability, and volume status, as well as suboptimal vascular access with temporary venous catheters. The impact of intermittent hemodialysis (IHD) versus continuous renal replacement therapy (CRRT) on outcomes in ARF is also not clear. Patient disease severity impacts more than dialysis modality in patient outcome, but when patients are stratified for equal disease severity, CRRT may have potential benefits over IHD in terms of patient survival, fluid and metabolic control, and renal recovery. Strategies associated with improved outcomes that have emerged thus far in ARF are to aim for a time-averaged blood urea nitrogen (BUN) of less than 60 mg/dl with IHD, varying IHD frequency as necessary, or to achieve a minimum ultrafiltration rate of 35 ml/kg/hr with CRRT.     

Multicenter clinical trial of recombinant human insulin-like growth factor I in patients with acute renal failure.

BACKGROUND: Patients with acute renal failure (ARF) have high morbidity and mortality rates, particularly if they have serious comorbid conditions. Several studies indicate that in rats with ARF caused by ischemia or certain nephrotoxins, insulin-like growth factor-I (IGF-I) enhances the recovery of renal function and suppresses protein catabolism. METHODS: Our objective was to determine whether injections of recombinant human IGF-I (rhIGF-I) would enhance the recovery of renal function and is safe in patients with ARF. The study was designed as a randomized, double-blind, placebo-controlled trial in intensive care units in 20 teaching hospitals. Seventy-two patients with ARF were randomized to receive rhIGF-I (35 patients) or placebo (37 patients). The most common causes of ARF in the rhIGF-I and placebo groups were, respectively, sepsis (37 and 35% of patients) and hypotension or hemodynamic shock (42 and 27% of patients). At baseline, the mean (+/- SD) APACHE II scores in the rhIGF-I and placebo-treated groups were 24 +/- 5 and 25 +/- 8, respectively. In the rhIGF-I and placebo groups, the mean (median) urine volume and urinary iothalamate clearances (glomerular filtration rate) were 1116 +/- 1037 (887) and 1402 +/- 1183 (1430) ml/24 hr and 6.4 +/- 5.9 (4.3) and 8.7 +/- 7.2 (4.4) ml/min and did not differ between the two groups. Patients were injected subcutaneously every 12 hours with rhIGF-I, 100 microgram/kg desirable body weight, or placebo for up to 14 days. Injections were started within six days of the onset of ARF. The primary end-point was a change in glomerular filtration rate from baseline. Other end points included changes from baseline in urine volume, creatinine clearance and serum urea, creatinine, albumin and transferrin, frequency of hemodialysis or ultrafiltration, and mortality rate. RESULTS: During the treatment period, which averaged 10.7 +/- 4.1 and 10.6 +/- 4.5 days in the rhIGF-I and placebo groups, there were no differences in the changes from baseline values of the glomerular filtration rate, creatinine clearance, daily urine volume, or serum urea nitrogen, creatinine, albumin or transferrin. In patients who did not receive renal replacement therapy, there was also no significant difference in serum creatinine and urea between the two groups. Twenty patients in the rhIGF-I group and 17 placebo-treated patients underwent dialysis or ultrafiltration. Twelve rhIGF-I-treated patients and 12 placebo-treated patients died during the 28 days after the onset of treatment. CONCLUSIONS: rhIGF-I does not accelerate the recovery of renal function in ARF patients with substantial comorbidity.     

Renal blood flow in experimental septic acute renal failure

Reduced renal blood flow (RBF) is considered central to the pathogenesis of septic acute renal failure (ARF). However, no controlled experimental studies have continuously assessed RBF during the development of severe septic ARF. We conducted a sequential animal study in seven female Merino sheep. Flow probes were implanted around the pulmonary and left renal arteries. Two weeks later, systemic hemodynamics and RBF were monitored continuously during a 48-h control period and, after a week, during a 48-h period of hyperdynamic sepsis induced by continuous Escherichia coli infusion. Infusion of E. coli induced hyperdynamic sepsis with significantly increased cardiac output (3.8+/-0.4 vs 9.8+/-1.1 l/min; P<0.05), decreased mean arterial pressure (89.2+/-3.2 vs 64.3+/-5.3 mm Hg; P<0.05), and increased total peripheral conductance (42.8+/-3.5 in controls vs 153.7+/-24.7 ml/min/mm Hg in septic animals; P<0.05). Hyperdynamic sepsis was associated with marked renal vasodilatation (renal conductance: 3.0+/-0.7 vs 11.4+/-3.4 ml/min/mm Hg; P<0.05) and a marked increase in RBF (262.3+/-47.7 vs 757.4+/-250.1 ml/min; P<0.05). Serum creatinine increased over 48 h (73+/-18 vs 305+/- micromol/l; P<0.05) whereas creatinine clearance decreased (95.5+/-25.9 vs 20.1+/-19.3 ml/min; P<0.05). After 24 h, urine output decreased from 1.4 to 0.3 ml/kg/h (P<0.05). Infusion of E. coli induced hyperdynamic sepsis and ARF. Septic ARF in this setting was associated with a marked increase in RBF and with renal vasodilatation.     

Acute renal failure in severely burned patients

Acute renal failure (ARF) is a well known complication of severe burns and is an important factor leading to an increase in mortality. In order to analyze possible pathogenetic and prognostic factors associated with ARF in burned patients we reviewed in a retrospective study the files of 328 patients with burns > 10% body surface area (BSA), admitted to our burn unit between 01.01.94 and 01.05.98. We found 48 patients with acute renal failure corresponding with an incidence of 14.6%. Patients with ARF had a mean burned surface area of 48% (13-95) and an abbreviated burn severity index score (ABSI) of 9.8 (4-15). Thirty eight (79%) of these patients had an inhalation injury diagnosed. Renal insufficiency was divided in a late and an early form depending on its time of onset and we found 15 (31%) patients with ARF occurring within the first 5 days of the hospital stay and 33 (69%) patients with ARF developing >5 days following the thermal injury. The incidence of myoglobinuria and hypotension during the resuscitation phase was significantly higher in the group with early ARF, whereas patients with late ARF presented sepsis more frequently than patients with early occurring renal failure. Accordingly, potential nephrotoxic antibiotics were administered more often in patients with late ARF. Patients with ARF were treated by continuous arteriovenous hemofiltration (CAVH) for a mean period of 10.5 days (1-47) and CAVH was associated with a complication rate of 10%. Most of the complications were associated with the vascular access in the femoral artery. The mortality rate in patients with ARF was 85% and death was due to multiple organ failure in 83% of the cases. Only burned BSA and inhalation injury proved to be significantly correlated with the development of ARF, whereas age, third degree burn or electric injury were not significantly different between the two groups. Neither age, TBSA, day of onset of ARF nor duration of the renal replacement therapy proved to be significantly different comparing survivors with non-survivors, and thus predictive for the survival rate.     

Continuous venovenous hemodialysis treatment in critically ill patients after liver transplantation

BACKGROUND: Acute renal failure (ARF) in critically ill patients is associated with a high mortality rate. Continuous renal replacement therapy (CRRT) is now widely used for the treatment of ARF in these critically ill patients. We retrospectively analyzed the role of CRRT as a prognostic parameter in patients receiving a cadaveric liver graft in 1998. METHODS: We reviewed the patient records of all adult recipients of a cadaveric liver graft (N = 54) in 1998 and compared those who underwent CRRT treatment (N = 19) to those without CRRT treatment (N = 35). RESULTS: Mortality was high in the continuous venovenous hemodialysis (CVVHD) group (58%). At the time of transplantation, creatinine (1.7+/-0.4 vs. 1.0+/-0.1 mg/dl), blood urea nitrogen (40+/-13 vs. 22+/-3 mg/dl), aspartate aminotransferase (ASAT; 585+/-420 vs. 242+/-97 U/liter), and bilirubin (11.6+/-4.1 vs. 6.5+/-1.9 mg/dl) were higher in the CVVHD group than in controls, whereas hemoglobin (10.3+/-0.6 vs. 10.8+/-0.4 g/dl), white blood cells (6.3+/-0.6 vs. 7.0+/-0.8/nl), and thrombocytes (110+/-18 vs. 90+/-10/nl) were similar. After transplantation, liver graft function was impaired in the CVVHD group as compared with controls. CONCLUSIONS: The necessity for CRRT in patients after liver transplantation correlates with a high risk of death. Thus, more efforts have to be made to prevent renal failure in patients after liver transplantation.     

Acute renal failure following massive mannitol infusion

Mannitol overuse-induced acute renal failure (ARF) has rarely been described. We report four cases, all male, between the ages of 20 and 42 years, who developed acute renal failure (3 anuric, 1 nonoliguric) after receiving mannitol 1,172 +/- 439 g (mean +/- SD) during a time period of 58 +/- 28 h. The infusion rate was 0.25 +/- 0.02 g/kg/h. The onset of acute renal failure was detected 48 +/- 22 h after infusion. In 2 of the 3 cases in which urinary cytology was evaluated, the presence of vacuole-containing renal tubular cells was observed. All patients had hyponatremia (120 +/- 11 mEq/l), and hyperosmolality (osmolar gap 70 +/- 11 mosm/kg water). No other factors could be pointed to as causing acute renal failure. In the 3 anuric cases in which hemodialysis was performed, immediate recovery of diuresis was observed. Two patients recovered renal function on the fifth and sixth days, and 2 died due to endocranial hypertension - one of them while recovering - on the fourth and sixth days. In the present report, mannitol-induced ARF occurred at clustered doses of 0.25 mg/kg/h.     

Low-dose prednisolone ameliorates acute renal failure caused by cholesterol crystal embolism

AIMS: The prognosis of renal cholesterol crystal embolism (CCE) is poor. Although various treatments for CCE have been attempted, there is no optimal therapy. We tested the effect of low-dose prednisolone (PS) on CCE-related acute renal failure (ARF). PATIENTS AND METHODS: 7 patients (mean age 69 years) diagnosed with CCE-related ARF were treated with oral PS at 15-20 mg/day for 2-4 weeks, which was then tapered at 5 mg/day over 2-4 weeks, followed by 5 mg/day maintenance dose. Recurrent ARF during PS tapering was treated with a larger dose of PS. RESULTS: Inciting factors were identified in four patients: coronary angiography (n=3) and cerebral angiography (n=1). On admission, serum creatinine (SCr) was 2.1 +/- 0.3 mg/dl (mean +/- SEM). SCr and eosinophil count before treatment were 4.2 +/- 0.4 mg/dl and 682 +/- 73/microl, respectively. PS therapy improved ARF in all cases at week 2 (SCr 3.8 +/- 0.5 mg/dl) parallel to a decrease in eosinophilia (116 +/- 30/microl), and at week 4 (3.1 +/- 0.4 mg/dl and 134 +/- 20/microl, respectively). At last follow-up, renal function was improved or maintained in 5 patients compared with that at week 4 post-treatment. One patient died of lung cancer. Another required LDL apheresis and hemodialysis but died due to CCE-related multi-organ failure. A third patient had recurrent ARF and was re-treated with a larger dose of PS, which resulted in an immediate decrease in SCr. However, the patient developed acute renal dysfunction due to congestive heart failure, and required hemodialysis. CONCLUSIONS: Low-dose PS improved CCE-related ARF, probably through amelioration of inflammatory reaction surrounding affected renal vessels.     

Dialysis modality and dosing strategy in acute renal failure

Many fundamental aspects of the management of renal replacement therapy (RRT) in acute renal failure (ARF) remain unresolved. While data from multiple studies support the initiation of RRT, in the absence of other indications, when the BUN has reached a level of approximately 90-100 mg/dl, there are conflicting data regarding the benefit of earlier initiation of renal support. The relative efficacy of the various RRT modalities is uncertain. Despite growing utilization, a survival benefit or greater recovery of renal function has not been demonstrated for continuous renal replacement therapy (CRRT) as compared to conventional intermittent hemodialysis (IHD). Optimal dosing strategies are also poorly defined. While there is increasing evidence that more intensive renal support is associated with better outcomes in ARF, an optimal Kt/Vurea and treatment frequency for IHD remain to be established. Similarly, although data suggest that continuous venovenous hemofiltration (CVVH) should be dosed at no less than 35 ml/kg/hr (postdilution), confirmation of this dosing strategy and validation for other modalities of CRRT are required.     

Efficacy and safety of renal tubule cell therapy for acute renal failure

The mortality rate for patients with acute renal failure (ARF) remains unacceptably high. Although dialysis removes waste products and corrects fluid imbalance, it does not perform the absorptive, metabolic, endocrine, and immunologic functions of normal renal tubule cells. The renal tubule assist device (RAD) is composed of a conventional hemofilter lined by monolayers of renal cells. For testing whether short-term (up to 72 h) treatment with the RAD would improve survival in patients with ARF compared with conventional continuous renal replacement therapy (CRRT), a Phase II, multicenter, randomized, controlled, open-label trial involving 58 patients who had ARF and required CRRT was performed. Forty patients received continuous venovenous hemofiltration + RAD, and 18 received CRRT alone. The primary efficacy end point was all-cause mortality at 28 d; additional end points included all-cause mortality at 90 and 180 d, time to recovery of renal function, time to intensive care unit and hospital discharge, and safety. At day 28, the mortality rate was 33% in the RAD group and 61% in the CRRT group. Kaplan-Meier analysis revealed that survival through day 180 was significantly improved in the RAD group, and Cox proportional hazards models suggested that the risk for death was approximately 50% of that observed in the CRRT-alone group. RAD therapy was also associated with more rapid recovery of kidney function, was well tolerated, and had the expected adverse event profile for critically ill patients with ARF.     

Survival of liver transplant candidates with acute renal failure receiving renal replacement therapy

BACKGROUND: Acute renal failure (ARF) in the setting of end-stage liver disease has a dismal prognosis without liver transplantation. Renal replacement therapy (RRT) is a common bridge to liver transplant despite a paucity of supportive data. We investigated our single-center patient population to determine efficacy of RRT in liver transplant candidates with ARF. METHODS: We identified 102 liver transplant candidates receiving RRT for ARF between April 30, 1999 and January 31, 2004. Patients that had initiated RRT intra- or postoperatively or received outpatient hemodialysis or peritoneal dialysis prior to admission were excluded. Survival to liver transplant, short-term mortality following liver transplant, and selected clinical characteristics were examined. RESULTS: Of patients who received RRT, 35% survived to liver transplant or discharge. Mortality was 94% in patients not receiving a liver and was associated with a higher Acute Physiological and Chronic Health Evaluation (APACHE) II, lower mean arterial pressure, and the use of continuous renal replacement therapy (CRRT). Patients receiving CRRT had greater severity of illness than those on hemodialysis. The 1-year mortality of patients initiating RRT prior to liver transplant was 30% versus 9.7% for all other liver recipients (P < 0.0045). CONCLUSION: RRT is justifiable for liver transplant candidates with ARF. Though mortality was high, a substantial percentage (31%) of patients survived to liver transplant. Postoperative mortality is increased compared with all other liver transplant recipients, but is acceptable considering the near-universal mortality without transplantation.     

Plasma leptin concentration in patients with acute renal failure

BACKGROUND: Acute renal failure (ARF) is characterized by impaired excretory, endocrine, homeostatic and metabolic function of the kidneys. It is well-known that leptin is an adipose-derived polypeptide hormone which is predominantly biodegraded by the kidneys. Therefore, plasma leptin concentration is increased in chronic renal failure (CRF). However, its' concentrations in patients with ARF were not investigated until now. The aim of the present study was to evaluate plasma leptin concentration in patients with ARF. PATIENTS AND METHODS: 27 patients with ARF (age 44 +/- 4 years, BMI 26.0 +/- 0.9 kg/m2, means +/- SEM, 17 patients 15 M, 2 F recovered kidney function and 10 patients 7 M, 3 F died during the anuric phase), 27 hemodialysis patients (22 M, 5 F; age 45 +/- 2 years; BMI 26.2 +/- 0.8 kg/m2) with chronic renal failure (CRF) and 27 healthy subjects (HS) (22 M, 5 F; age 42 +/- 3 years; BMI 25.9 +/- 0.6 kg/m2) were examined. In patients with ARF, blood samples for plasma leptin and routinely assessed biochemical parameters were withdrawn before the first HD session (I), and in patients who survived a second time 5 days later during the anuric/oliguric phase (II), and a third one during the polyuric phase before discharge of the patient from hospital (III). In patients with CRF all examined parameters were estimated only once before a subsequent HD session. RESULTS: Patients with ARF (before the first HD session) and CRF did not differ significantly with respect to BMI, serum creatinine and blood hydrogen ion concentrations. Plasma leptin level in patients with ARF before the first HD session was similar to values obtained in HS, but significantly lower (p < 0.01) than in patients with CRF (2.5 (1.9 - 8.2) vs. 3.4 (2.5 - 8.3) vs. 8.4 (2.9 - 16.9) ng/ml in ARF, HS and CRF, respectively). There was no significant difference in leptinemia between patients with ARF who survived and who died. In patients with ARF who survived, improvement ofrenal function was accompanied by a slightly (not significant) declining tendency in plasma leptin concentration (5.6 +/- 2.2 vs. 4.8 +/- 1.7 vs. 4.5 +/- 1.3 ng/ml; I, II, III phases of ARF, respectively). CONCLUSIONS: In contrast to hemodialysis patients with chronic renal failure, patients with acute renal failure are characterized by normal plasma leptin concentration. Thus, difference in leptinemia between patients with chronic and acute renal failure seems to be due to preservation of large amounts of active renal parenchyma in ARF patients.     

Acute renal failure in the neonatal period

Acute renal failure (ARF) is a common problem in the neonatal intensive care unit (NICU). In most cases, ARF is associated with a primary condition such as sepsis, metabolic diseases, perinatal asphyxia and/or prematurity. This retrospective study investigated the course of illness, therapeutic interventions, early prognosis and risk factors associated with development of ARF in the neonatal period. A total of 1311 neonates were treated in our NICU during the 42-month study period, and 45 of these babies had ARF. This condition was defined as serum creatinine level above 1.5 mg/dL despite normal maternal renal function. The data collected for each ARF case were contributing condition, cause and clinical course of ARF, gestational age and birth weight, age at the time of diagnosis, treatment, presence of perinatal risk factors and need for mechanical ventilation. The frequency of ARF in the NICU during the study period was 3.4%. Premature newborns constituted 31.1% of the cases. The mean birth weight in the group was 2863 +/- 1082 g, and the mean age at diagnosis was 6.2 +/- 7.4 days. The causes of ARF were categorized as prerenal in 29 patients (64.4%), renal in 14 patients (31.1%) and postrenal in 2 patients (4.4%). Forty-seven percent of the cases were nonoliguric ARF. Asphyxia was the most common condition that contributed to ARF (40.0%), followed by sepsis/metabolic disease (22.2%) and feeding problems (17.8%). Therapeutic interventions were supportive in 77.8% of the cases, and dialysis was required in the other 22.2%. The mortality rate in the 45 ARF cases was 24.4%. Acute renal failure of renal origin, need for dialysis, and need for mechanical ventilation were associated with significantly increased mortality (p<0.05). There were no statistical correlations between mortality rate and perinatal risk factors, oliguria, prematurity or blood urea nitrogen and creatinine levels. The study showed that, at our institution, ARF in the neonatal period is frequently associated with preventable conditions, specifically asphyxia, sepsis and feeding problems. Supportive therapy is effective in most cases of neonatal ARF. Acute renal failure of renal origin, need for dialysis, and need for mechanical ventilation were identified as indicators of poor prognosis in these infants. Early recognition of risk factors and rapid effective treatment of contributing conditions will reduce mortality in neonatal ARF.