Efficacy and safety of Amphotericin B Lipid Complex Injection (ABLC) in solid-organ transplant recipients with invasive fungal infections

Background: Fungal infections following solid-organ transplantation are a major source of morbidity and mortality. This report describes the efficacy and safety of Amphotericin B Lipid Complex Injection (ABLC) in solid-organ transplant recipients.
Methods: Three open-label, second-line treatment studies evaluated ABLC as a treatment for severe, life-threatening mycoses in patients who were refractory to or intolerant to conventional antifungal (mostly amphotericin B [AmB]) therapy or had pre-existing renal disease.
Results: The 79 solid-organ transplant recipients (25 heart, 20 liver, 17 kidney, 11 lung, 5 multiple, 1 pancreas) who received ABLC in these studies had the following fungal infections: aspergillosis (n=39); candidiasis (n=20); zygomycosis (n=8); cryptococcosis and histoplasmosis (n=3 each); and blastomycosis, cladosporiosis, fusariosis, Bipolaris hawaiiensis , Dactylaria gallopava , and an unspecified fungal infection (n=1 each). The median duration of ABLC therapy was 28 d (1–178 d). The daily dose ranged between 1.6 and 7.4 mg/kg (median, 4.6 mg/kg). The clinical response rate for the patients who could be assessed was 58% (39/67). Clinical response rates for heart, liver, kidney, and lung recipients were 59, 60, 67, and 40%, respectively; response rates for aspergillosis and candidiasis were 47 and 71%, respectively. Forty-six of the 79 patients (58%) survived for more than 28 d after the last dose of ABLC. Mean baseline serum creatinine was 3.2 mg/dL; 64 patients (81%) had stable (n=37) or improved (n=27) serum creatinine at the end of treatment.
Conclusions: ABLC is safe and effective treatment for fungal infections in solid-organ transplant recipients. Its renal-sparing properties are particularly suited for this high-risk population for renal failure.     

Comparative safety of amphotericin B lipid complex and amphotericin B deoxycholate as aerosolized antifungal prophylaxis in lung-transplant recipients

BACKGROUND: Aerosolized administrations of amphotericin B deoxycholate (AmBd) and amphotericin B lipid complex (ABLC) in lung transplant recipients were compared for safety and tolerability. The incidence of invasive fungal infections in patients receiving aerosolized amphotericin B formulations as sole prophylaxis was determined. METHODS: A prospective, randomized (1:1), double-blinded trial was conducted with 100 subjects. AmBd and ABLC were administered postoperatively by nebulizer at doses of 25 mg and 50 mg, respectively, which were doubled in mechanically ventilated patients. The planned treatment was once every day for 4 days, then once per week for 7 weeks. Treatment-related adverse events and invasive fungal infections were quantitated for 2 months after study drug initiation. RESULTS: Intent-to-treat analysis revealed study drug was discontinued for intolerance in 6 of 49 (12.2%) and 3 of 51 (5.9%) patients in the AmBd- and ABLC-treated groups, respectively (p=0.313). Subjects receiving AmBd were more likely to have experienced an adverse event (odds ratio 2.16, 95% confidence interval 1.10, 4.24, p=0.02). Primary prophylaxis failure within 2 months of study drug initiation was observed in 7 of 49 (14.3%) AmBd-treated patients and 6 of 51 (11.8%) ABLC-treated patients. No fungal pneumonias were observed. Only two (2%) patients experienced documented primary prophylaxis failure with Aspergillus infections within the follow-up period. CONCLUSIONS: Both aerosol AmBd and ABLC appear to be associated with a low rate of invasive pulmonary fungal infection in the early posttransplant period. Patients receiving ABLC were less likely to experience a treatment-related adverse event.     

Fenoldopam infusion for renal protection in high-risk cardiac surgery patients: a randomized clinical study

OBJECTIVE: The purpose of this study was to evaluate the renoprotective effects of fenoldopam in patients at high risk of postoperative acute kidney injury undergoing elective cardiac surgery requiring cardiopulmonary bypass. DESIGN: A double-blind randomized clinical trial. Setting: Hospital. Participants: One hundred ninety-three patients. Interventions: Patients undergoing cardiac surgery were randomly assigned to receive a continuous infusion of fenoldopam, 0.1 microg/kg/min (95 patients), or placebo (98 patients) for 24 hours. Patients were included if at least 1 of the following risk factors was present: preoperative serum creatinine > or =1.5 mg/dL, age >70 years, diabetes mellitus, or prior cardiac surgery. Serum creatinine and urinary output were measured at baseline (T1), 24 hours (T2), and 48 hours after surgery (T3). Acute kidney injury was defined as a postoperative serum creatinine level of > or =2 mg/dL with an increase in serum creatinine level of 0.7 mg/dL or greater from preoperative to maximum postoperative values. MEASUREMENTS AND MAIN RESULTS: Acute kidney injury developed in 12 of 95 (12.6%) patients receiving fenoldopam and in 27 of 98 (27.6%) patients receiving placebo (p = 0.02), whereas renal replacement therapy was started in 0 of 95 and 8 of 98 (8.2%) patients, respectively (p = 0.004). Serum creatinine was similar at baseline (1.8 +/- 0.4 mg/dL v 1.9 +/- 0.3 mg/dL) in the fenoldopam and placebo groups but differed significantly (p < 0.001 and p < 0.001) 24 hours (1.6 +/- 0.2 mg/dL v 2.5 +/- 0.6 mg/dL) and 48 hours (1.5 +/- 0.3 mg/dL v 2.8 +/- 0.4 mg/dL) after the operation. CONCLUSIONS: A 24-hour infusion of 0.1 mug/kg/min of fenoldopam prevented acute kidney injury in a high-risk population undergoing cardiac surgery.     

Renal safety of adefovir dipivoxil in patients with chronic hepatitis B: two double-blind, randomized, placebo-controlled studies

BACKGROUND: The incidence of adefovir dipivoxil (ADV) nephrotoxicity has been previously reported with the 60 and 120 mg daily dose in human immunodeficiency virus (HIV). We report a complete analysis on the renal tolerance of ADV at the currently approved dose of 10 mg daily for the treatment of chronic hepatitis B. METHODS: To investigate the efficacy, safety, and the tolerability of two dosing regimens of ADV (10 mg daily or 30 mg daily), two double-blind, placebo-controlled studies were performed in patients with chronic hepatitis B and compensated liver disease who were not undergoing current treatment and who had evidence of hepatitis B virus (HBV) replication. RESULTS: There was no overall median change from baseline at week 48 in serum creatinine or serum phosphorus levels in the ADV 10 mg group. In the ADV 30 mg group there was a slight increase of 0.2 mg/dL in median serum creatinine levels, and decrease of 0.1 mg/dL in serum phosphorus levels at week 48. Serum creatinine increase and hypophosphatemia were more frequently observed in patients receiving ADV 30 mg daily compared with ADV 10 mg and placebo. There were no grade 4 proteinuria, hematuria, or glycosuria events. CONCLUSION: Mild nephrotoxicity was demonstrated with the dose of 30 mg daily. Nephrotoxicity, as defined by an increase >/=0.5 mg/dL from baseline in serum creatinine or a serum phosphorus value of <1.5 mg/dL on two consecutive occasions, was not observed in patients treated with ADV 10 mg for a median follow-up period of approximately 64 weeks.     

A randomized prospective trial of amphotericin B lipid emulsion versus dextrose colloidal solution in critically ill patients.

BACKGROUND: Amphotericin B is the agent of choice for most invasive fungal infections in critically ill patients. It is associated with at least a 50% incidence of nephrotoxicity, despite prophylactic measures such as sodium loading. Newer formulations of amphotericin B are available but are costly and have unknown bioavailability in critically ill patients. Previous trials in neutropenic and critically ill patients have demonstrated that mixing amphotericin B with 20% lipid solution (Intralipid; Clintec Nutrition, Deerfield, III) may decrease nephrotoxicity. METHODS: In this randomized, prospective clinical trial, patients with positive fungal blood cultures, tracheal/sputum cultures or peritoneal cavity cultures were randomized to receive either 0.5 mg/kg per day of amphotericin B dextrose or 1.0 mg/kg per day of amphotericin B lipid emulsion. Duration of therapy was determined by the primary care team. Weekly 24-hour creatinine clearance was measured until 2 weeks after amphotericin B therapy was completed. RESULTS: The two groups were similar based on age, white blood cell count, serum creatinine, and creatinine clearance at the beginning of therapy. The group receiving amphotericin B lipid emulsion had significantly less decrease in creatinine clearance compared with controls, despite receiving significantly more amphotericin B. CONCLUSION: Amphotericin B lipid emulsion can be given at a higher total cumulative dose than amphotericin B dextrose with less nephrotoxicity.     

Treating anemia early in renal failure patients slows the decline of renal function: a randomized controlled trial

BACKGROUND: Erythropoietin is known to improve outcomes in patients with anemia from chronic renal disease. However, there is uncertainty about the optimal timing of initiation of erythropoietin treatment in predialysis patients with non-severe anemia. METHODS: We conducted a randomized controlled trial of early versus deferred initiation of erythropoietin in nondiabetic predialysis patients with serum creatinine 2 to 6 mg/dL and hemoglobin 9 to 11.6 g/dL. The early treatment arm was immediately started on 50 U/kg/wk of erythropoietin alpha with appropriate titration aiming for hemoglobin of > or =13 g/dL. The deferred treatment arm would start erythropoietin only when hemoglobin decreased to <9 g/dL. The primary end point was a composite of doubling of creatinine, renal replacement, or death. RESULTS: Eighty-eight patients were randomized (early treatment N= 45, deferred treatment N= 43) and followed for a median of 22.5 months. During follow-up, 13 versus 23 patients reached the primary end point in the two arms, respectively (log-rank P= 0.0078). The relative hazard for reaching an end point was 0.42 (P= 0.012). Adjusting for baseline serum creatinine, the adjusted relative hazard was 0.37 (P= 0.004), while the risk increased 2.23-fold (P < 0.001) per 1 mg/dL higher creatinine at baseline. The benefit was similar regardless of the baseline hemoglobin and proteinuria. No patients had any severe adverse events. CONCLUSION: Early initiation of erythropoietin in predialysis patients with non-severe anemia significantly slows the progression of renal disease and delays the initiation of renal replacement therapy.     

Prospective study of atrial natriuretic peptide for the prevention of radiocontrast-induced nephropathy

Radiocontrast-induced nephropathy (RCIN) is a common cause of hospital-acquired acute renal failure and is associated with a high mortality rate. RCIN is potentially preventable, because administration of the radiocontrast agent is predictable, and a high-risk population has been identified. This multicenter, prospective, randomized, double-blind, placebo-controlled trial was performed to evaluate the efficacy of intravenous atrial natriuretic peptide (anaritide, ANP 4-28) to prevent RCIN. Patients with stable chronic renal failure (serum creatinine greater than 1.8 mg/dL or serum creatinine between 1.5 and 1.8 mg/dL with estimated creatinine clearance of < or = 65 mL/min) were assigned to receive either placebo or one of three doses of anaritide (0.01 microg/kg/min, 0.05 microg/kg/min, or 0.1 microg/kg/min) for 30 minutes before and continuing for 30 minutes after radiocontrast administration. All patients were given intravenous 0.45% saline for 12 hours before the radiocontrast procedure and continuing for 12 hours after the last dose of radiocontrast. Both ionic and nonionic radiocontrast agents were administered. RCIN was defined as either an absolute increase of serum creatinine of > or = 0.5 mg/dL or a percent increase of > or = 25% over baseline. Of the 247 patients who completed the study, 50% had diabetes mellitus. There were no statistical differences in baseline serum creatinine, change in serum creatinine, or the incidence of RCIN. The incidence of RCIN was placebo, 19%; anaritide (0.01), 23%; anaritide (0.05), 23%; anaritide (0.1), 25%. Patients with diabetes mellitus had a significantly greater incidence of RCIN: placebo, 26% versus 9%; anaritide (0.01), 33% versus 13%; anaritide (0.05), 26% versus 21%; anaritide (0.1), 39% versus 8% (diabetic v nondiabetic, P < 0.002). There was no effect in the diabetic or nondiabetic groups by anaritide on the incidence of RCIN. Comparison of the highest-risk group of patients, defined as patients with diabetes mellitus and a baseline serum creatinine > or = 1.8 mg/dL, with the lowest-risk group, defined as patients without diabetes mellitus and a baseline serum creatinine of 1.8 mg/dL or less, did not show a beneficial effect of anaritide administration. In conclusion, administration of intravenous anaritide before and during a radiocontrast study did not reduce the incidence of RCIN in patients with preexisting chronic renal failure, with or without diabetes mellitus.     

Correlates of acute renal failure in patients receiving parenteral amphotericin B

BACKGROUND: While parenteral amphotericin B is an effective therapy for serious fungal infections, it frequently causes acute renal failure (ARF). This study identified correlates of ARF in amphotericin B therapy and used them to develop clinical prediction rules. METHODS: All 643 inpatients receiving parenteral amphotericin B therapy at one tertiary care hospital were included. Data regarding correlates were obtained both electronically and from manual chart review in a subsample of 231 patients. ARF was defined as a 50% increase in the baseline creatinine with a peak > or =2.0 mg/dL. RESULTS: Among 643 episodes, ARF developed in 175 (27%). In the larger group, the only independent correlate of ARF was male gender (OR = 2.2, 95% CI, 1.5 to 3.3). In the subsample (N = 231), independent correlates of ARF were maximum daily amphotericin dosage, location at the time of initiation of amphotericin therapy, and concomitant use of cyclosporine. These data were used to develop two clinical prediction rules. A rule using only data available at initiation of therapy stratified patients into groups with probability of ARF ranging from 15 to 54%, while a rule including data available during therapy (maximum daily dose) stratified patients into groups with probability of ARF ranging from 4 to 80%. CONCLUSIONS: Acute renal failure occurred in a quarter of the patients. Correlates of ARF at the beginning and during the course of amphotericin therapy were identified and then combined to allow stratification according to ARF risk. These data also provide evidence for guidelines for the selection of patients for alternative therapies.     

Renal function after cardiac surgery: adverse effect of furosemide

Renal failure is a frequent event after cardiopulmonary by-pass. Hemodynamic alterations that occur during surgery, as well as factors depending on the host, are the main risk factors for renal dysfunction. To evaluate the frequency and risk factors for renal dysfunction in this setting, a cohort of fifty patients with preoperative serum creatinine under 1.5 mg/dL, submitted to cardiac surgery with cardiopulmonary by-pass was analyzed. Variables related to preoperative patient condition, intraoperative and postoperative periods were recorded. Renal function was assessed by clearances of creatinine, urea and free water, also by fractional excretion of sodium (FENa), at baseline, at anesthetic induction and during postoperative period. Patients were arbitrarily divided in two groups, according to the serum creatinine (S(Cr)) value at the end of the postoperative period: Group 1: S(Cr) < 2 mg/dL (n = 44 patients (88.5%)) and Group II: S(Cr) > 2 mg/dL (n = 6 patients (11.5%)). A decrease of renal function was observed in all patients: creatinemia raised from 1.04 +/- 0.2 to 1.55 +/- 0.4 mg/dL (33%), associated with a rise in FENa. Differences between group I and group II using univariate analysis were: baseline serum creatinine (1.01 +/- 0.23 mg/dL vs. 1.26 +/- 0.19 mg/dL, p = 0.03), FENa (0.99 +/- 0.8 vs. 2.2 +/- 2.1, p = 0.04), furosemide dose during surgery normalized to body surface area (93.2 +/- 23 mg/1.73 m2 BSA vs. 135 +/- 38 mg/1.73 m2 BSA, p < 0.001), and hemodilution index (17.3 +/- 4.3% vs. 22.8 +/- 3.2%, p < 0.01). In the multiple regression model, baseline creatinemia and furosemide dose were associated to renal dysfunction.     

Modest serum creatinine elevation affects adverse outcome after general surgery

BACKGROUND: Modest preoperative serum creatinine elevation (1.5 to 3.0 mg/dL) has been recently shown to be independently associated with morbidity and mortality after cardiac surgery. It is important to know if this association can be applied more broadly to general surgery cases. METHODS: Multivariable logistic regression analyses of 46 risk variables in 49,081 cases from the Veterans Affairs National Surgical Quality Improvement Program, undergoing major general surgery from 10/1/96 through 9/30/98. RESULTS: Thirty day mortality and several cardiac, respiratory, infectious and hemorrhagic morbidities were significantly (P < 0.001) higher in patients with a serum creatinine>1.5 mg/dL. With multivariable analysis, the adjusted odds ratio for mortality for patients with a serum creatinine of 1.5 to 3.0 mg/dL was 1.44 [95% confidence interval (95% CI) 1.22 to 1.71] and for creatinine>3.0 mg/dL was 1.93 (95% CI 1.51 to 2.46). The adjusted odds ratio for morbidity (one or more postoperative complications) for patients with a serum creatinine of 1.5 to 3.0 mg/dL was 1.18 (95% CI 1.06 to 1.32) and for creatinine>3.0 mg/dL was 1.19 (95% CI 0.99 to 1.43). Further stratification and recursive partitioning of creatinine levels revealed that a serum creatinine level>1.5 mg/dL was the approximate threshold for both increased morbidity and mortality. CONCLUSIONS: Modest preoperative serum creatinine elevation (>1.5 mg/dL) is a significant predictor of risk-adjusted morbidity and mortality after general surgery. A preoperative serum creatinine of 1.5 mg/dL or higher is a readily available marker for potential adverse outcomes after general surgery.     

Long-term effects of ureteroscopic laser lithotripsy on glomerular filtration rate in the face of mild to moderate renal insufficiency.

BACKGROUND AND PURPOSE: Ureteroscopic laser treatment of calculi in the upper urinary tract was examined in regard to its effect on renal function in the setting of mild renal insufficiency. Percutaneous nephrolithotomy (PCNL) and SWL have been previously shown not to adversely affect the glomerular filtration rate (GFR) in renal insufficiency, but to our knowledge, the effect of ureteroscopic laser lithotripsy on GFR has not been previously reported. PATIENTS AND METHODS: A retrospective review of all cases of ureteroscopic laser lithotripsy at our institution was performed. A total of 18 patients with a baseline serum creatinine of > or = 1.5 mg/dL were found. The mean follow-up after treatment was 18.0 months (range 4-39 months). The change in the reciprocal of serum creatinine was used as an indicator of change in the GFR. Deterioration of 20% was considered significant. RESULTS: The overall mean change in treated patients was a 5.9% improvement. Patients with a preoperative creatinine of < 2.0 mg/dL improved 7.6% and those with creatinine of > or = 2.0 mg/dL increased 3.9%. Other factors such as the size of the stone, location of the stone, and total joules used during treatment were not significant. CONCLUSION: This examination suggests that ureteroscopic laser lithotripsy has no ill effects on renal function in the face of mild to moderate renal insufficiency.     

Effect of amphotericin B lipid complex (ABLC) in very low birth weight infants

The aim of this retrospective, case-control study was to determine the effect of the amphotericin B lipid complex (ABLC) on serum creatinine (SCr), blood urea nitrogen (BUN), sodium (Na), and potassium (K) in very low birth weight (VLBW) infants. Medical records of all VLBW infants who were admitted to our Neonatal Intensive Care Unit between May 1998 and May 2006 and had received ABLC for at least 2 weeks were reviewed for patient demographics, use of medications (ABLC, diuretics, xanthines, indomethacin, vancomycin, gentamicin, pressors, and inotropes), fluid intake, urinary output, and serum electrolytes. Thirty-five patients who received ABLC were identified and matched by gestational age (GA) to 35 patients who served as controls. Infants who received ABLC had an average GA of 25.7 +/- 2.1 weeks and a birth weight of 764 +/- 196 g. Between day 1 and 14 of ABLC treatment, the BUN decreased from 17.5 +/- 11.5 to 10.5 +/- 6.8 mg/dl (p = 0.01), the SCr varied between 0.78 +/- 0.32 and 0.69 +/- 0.32 mg/dl, Na varied between 136.6 +/- 5.8 and 137.8 +/- 3.6 mEq/l, and K varied between 4.8 +/- 0.9 and 4.9 +/- 0.6 mEq/l, respectively. Based on these results, we conclude that treatment with ABLC for 2 weeks did not increase BUN or SCr, nor decrease Na or K in VLBW infants.     

ACE gene D/D genotype as a risk factor for chronic nephrotoxicity from calcineurin inhibitors in liver transplant recipients

BACKGROUND: Chronic renal failure (CRF) is a major cause of morbidity and mortality after orthotopic liver transplantation (OLTX) and is predominantly caused by calcineurin inhibitors (CI)-induced nephrotoxicity. The activation of the renin angiotensin system (RAS) has been implicated in the pathogenesis of chronic nephrotoxicity from CI. METHODS: We retrospectively investigated the genes coding for components of the RAS (ACE gene, Angiotensin II receptor 1 gene, Angiotensinogen gene) in 233 liver transplant recipients receiving Cyclosporine (CsA) or Tacrolimus (Tac) as maintenance immunosuppressant. All patients with serum creatinine (sCr) <1.0 mg/dL (n=143) before orthotopic liver transplantation (OLTX) were included in the final analysis. Patients were than categorized into two groups based upon their most recent postliver transplant sCr level: Group 1 (n=83) with sCr <1.5 mg/dL (mean 1.1+/-0.2) and group 2 (n=60) with sCr > or =1.5 mg/dL (mean 2.5+/-1.3) RESULTS: ACE D/D genotype was found in 57% of patients with sCr > or =1.5 mg/dL compared to 20% of patients with sCr <1.5 mg/dL (P<0.0001) CONCLUSIONS: Our analysis strongly suggests that liver transplant patients with ACE gene D/D genotype are at a significant higher risk of developing CI-induced chronic nephrotoxicity.     

Impact of renal function on efficacy of extracorporeal shockwave lithotripsy

BACKGROUND AND PURPOSE: Adequate urine production and excretion may be important for clearance of stone fragments after extracorporeal shockwave lithotripsy (SWL). This study evaluated the impact of renal function, measured by preoperative serum creatinine concentration, on the efficacy of SWL. PATIENTS AND METHODS: From 1986 to 2001, 27,299 patients with urolithiasis were treated with Medstone STS lithotripters. Seven hundred ninety-eight of these patients (2.92%) had serum creatinine concentrations >or=2.0 mg/dL. Perioperative renal function (serum creatinine), treatment parameters, stone-free success rate (no residual fragments on plain film), and perioperative complications and procedures were recorded. RESULTS: The stone-free rate for patients with serum creatinine values from 2.0 to 2.9 mg/dL (56.69%) was significantly less than that seen in patients with a creatinine concentration <2.0 mg/dL (66.20%). The retreatment rate and secondary-procedure rate were significantly higher in patients with higher serum creatinine values (9.62% and 8.92%, respectively) than in those with serum creatinine within the normal range (6.07% and 4.27%, respectively). There was no significant difference in the stone-free rate, re-treatment rate, and secondary-procedure rate of patients with serum creatinine >or=3.0 mg/dL in comparison with patients with values <2 mg/dL. Complication rates were higher for patients with serum creatinine values >4.0 mg/dL (10.91%) than for patients with creatinine <2.0 mg/dL (2.62%). CONCLUSIONS: The efficacy of SWL is decreased in patients with serum creatinine concentrations of 2.0 to 2.9 mg/dL, and the complication rate is higher in patients with serum creatinine >4.0 mg/dL. Preoperative counseling may include a discussion of the impact of renal insufficiency on success and complication rates associated with SWL.     

Percutaneous nephrolithotomy requiring multiple tracts: comparison of morbidity with single-tract procedures

PURPOSE: To compare the morbidity of percutaneous nephrolithotomy (PCNL) requiring multiple percutaneous tracts with that of procedures requiring a single tract for calculus clearance. PATIENTS AND METHODS: Data from 20 patients undergoing PCNL through two or more percutaneous renal tracts over a 1-year period were compared with a contemporary cohort of 20 patients undergoing PCNL requiring a single tract. The mean stone size was 2157 mm(2) v 423 mm(2) (P < 0.0001), the baseline serum creatinine concentration was 1.67 mg/dL v 1.13 mg/dL (P < 0.05), and the baseline hemoglobin concentration was 11.8 g/dL v 13.4 g/dL (P < 0.05) in the multiple- and single-tract groups, respectively. RESULTS: All single-tract and 95% of multiple-tract patients were rendered stone free. The mean drop in hemoglobin was similar in the two groups (2.3 g/dL for single tract v 2.1 g/dL for multiple tracts; P = 0.55). Complications occurred in two patients in each group. Four multiple-tract patients required blood transfusion. The need for transfusion correlated with lower preoperative hemoglobin and higher preoperative serum creatinine. There was a significant rise in serum creatinine (1.67 mg/dL to 1.91 mg/dL; P < 0.05) and drop in creatinine clearance (76.9 mL/min to 67.2 mL/min; P < 0.05) in the multiple-tract group; this was more pronounced in patients with existing renal insufficiency. No significant change in renal function was seen in the single-tract group. CONCLUSIONS: Monotherapy with PCNL utilizing multiple percutaneous tracts is highly effective in the treatment of staghorn and other large-volume renal calculi. Blood loss and complication rates with such an aggressive approach are comparable to those of PCNL incorporating a single percutaneous tract for more straightforward calculi.     

The Renal Safety Profile of Fluvastatin: Results of a Pooled Analysis

A pooled analysis was designed to evaluate the effects of fluvastatin on the kidney, in terms of renal adverse events, laboratory abnormalities, and renal function over time. An analysis of adverse events was performed on data from 30 completed clinical trials of fluvastatin in 11,815 patients. An analysis of renal function was also performed on data from patients who participated in long-term studies >6 months in treatment duration. Creatinine clearance was calculated using the Cockcroft-Gault formula. Mean creatinine clearance values were in the normal to near-normal range at baseline. Changes in creatinine clearance and serum creatinine from baseline were similar in fluvastatin-treated patients and placebo-treated patients. In the all-fluvastatin group, mean creatinine clearance (±standard deviation) increased from 87.8 (±42.8) mL/min at baseline to 89.4 (±41.2) mL/min at endpoint. In the placebo group, mean creatinine clearance (± standard deviation) increased from 87.7 (± 43.9) mL/min at baseline to 88.7 (±41.4) mL/min at endpoint. In the all-fluvastatin group, mean serum creatinine (± standard deviation) decreased from 1.14 (±0.20) mg/dL at baseline to 1.11 (±0.20) mg/dL at endpoint. In the placebo group, mean serum creatinine (±standard deviation) decreased from 1.15 (±0.22) mg/dL at baseline to 1.12 (±0.22) mg/dL at endpoint. The incidence of renal adverse events was low and comparable between the fluvastatin and placebo treatment groups. This pooled analysis demonstrates that fluvastatin treatment across the approved daily dose range of 20 mg to 80 mg does not adversely affect creatinine or creatinine clearance over time in dyslipidemic patients.     

Renal failure predisposes patients to adverse outcome after coronary artery bypass surgery. VA Cooperative Study #5

BACKGROUND: More than 600,000 coronary artery bypass graft (CABG) procedures are done annually in the United States. Some data indicate that 10 to 20% of patients who are undergoing a CABG procedure have a serum creatinine of more than 1.5 mg/dl. There are few data on the impact of a mild increase in serum creatinine concentration on CABG outcome. METHODS: We analyzed a Veterans Affairs database obtained prospectively from 1992 through 1996 at 14 of 43 centers performing heart surgery. We compared the outcome after CABG in patients with a baseline serum creatinine of less than 1.5 mg/dl (median 1.1 mg/dl, N = 3271) to patients with a baseline serum creatinine of 1.5 to 3.0 mg/dl (median 1.7, N = 631). RESULTS: Univariate analysis revealed that patients with a serum creatinine of 1.5 to 3.0 mg/dl had a higher 30-day mortality (7% vs. 3%, P < 0.001) requirement for prolonged mechanical ventilation (15% vs. 8%, P = 0.001), stroke (7% vs. 2%, P < 0.001), renal failure requiring dialysis at discharge (3% vs. 1%, P < 0.001), and bleeding complications (8% vs. 3%, P < 0.001) than patients with a baseline serum creatinine of less than 1.5 mg/dl. Multiple logistic regression analyses found that patients with a baseline serum creatinine of less than 1.5 mg/dl had significantly lower (P < 0.02) 30-day mortality and postoperative bleeding and ventilatory complications than patients with a serum creatinine of 1.5 to 3.0 mg/dl when controlling for all other variables. CONCLUSION: These results demonstrate that mild renal failure is an independent risk factor for adverse outcome after CABG.     

Grade of chronic renal failure,and acute and long-term outcome after percutaneous coronary interventions

BACKGROUND: Patients with moderate chronic renal failure have recently been identified to suffer from a markedly higher mortality after percutaneous coronary intervention (PCI). We focused on the outcome of PCI patients with just mildly elevated creatinine levels of 1.1 to 1.5 mg/dL. METHODS: Data of all PCI patients of the years 1998 to 1999 were analyzed. Follow-up was performed by a questionnaire sent to all patients. RESULTS: During this period, PCI was performed in 1049 patients. Long-term follow-up (1184 +/- 10 days) was 99.6% complete. Total mortality increased continuously by each creatinine increment of 0.1 mg/dL above 1.0 mg/dL, with a significant difference at 1.3 mg/dL compared to patients with 相似文献   

Tacrolimus with Mycophenolate Mofetil (MMF) or Sirolimus vs. Cyclosporine with MMF in Cardiac Transplant Patients: 1-Year Report

The most advantageous combination of immunosuppressive agents for cardiac transplant recipients has not yet been established. Between November 2001 and June 2003, 343 de novo cardiac transplant recipients were randomized to receive steroids and either tacrolimus (TAC) + sirolimus (SRL), TAC + mycophenolate mofetil (MMF) or cyclosporine (CYA) + MMF. Antilymphocyte induction therapy was allowed for up to 5 days. The primary endpoint of >/=3A rejection or hemodynamic compromise rejection requiring treatment showed no significant difference at 6 months (TAC/MMF 22.4%, TAC/SRL 24.3%, CYA/MMF 31.6%, p = 0.271) and 1 year (p = 0.056), but it was significantly lower in the TAC/MMF group when compared only to the CYA/MMF group at 1 year (23.4% vs. 36.8%; p = 0.029). Differences in the incidence of any treated rejection were significant (TAC/SRL = 35%, TAC/MMF = 42%, CYA/MMF = 59%; p < 0.001), as were median levels of serum creatinine (TAC/SRL = 1.5 mg/dL, TAC/MMF = 1.3 mg/dL, CYA/MMF = 1.5 mg/dL; p = 0.032) and triglycerides (TAC/SRL = 162 mg/dL, TAC/MMF = 126 mg/dL, CYA/MMF = 154 mg/dL; p = 0.028). The TAC/SRL group encountered fewer viral infections but more fungal infections and impaired wound healing. These secondary endpoints suggest that the TAC/MMF combination appears to offer more advantages than TAC/SRL or CYA/MMF in cardiac transplant patients, including fewer >/=3A rejections or hemodynamic compromise rejections and an improved side-effect profile.     

Renal Function After Cardiac Surgery: Adverse Effect of Furosemide

Renal failure is a frequent event after cardiopulmonary by-pass. Hemodynamic alterations that occur during surgery, as well as factors depending on the host, are the main risk factors for renal dysfunction. To evaluate the frequency and risk factors for renal dysfunction in this setting, a cohort of fifty patients with preoperative serum creatinine under 1.5 mg/dL, submitted to cardiac surgery with cardiopulmonary by-pass was analyzed. Variables related to preoperative patient condition, intraoperative and postoperative periods were recorded. Renal function was assessed by clearances of creatinine, urea and free water, also by fractional excretion of sodium (FENa), at baseline, at anesthetic induction and during postoperative period. Patients were arbitrarily divided in two groups, according to the serum creatinine (S_Cr) value at the end of the postoperative period: Group I: S_Cr <2 mg/dL (n = 44 patients (88.5%)) and Group II: S_Cr >2 mg/dL (n = 6 patients (11.5%)). A decrease of renal function was observed in all patients: creatinemia raised from 1.04 ± 0.2 to 1.55 ± 0.4 mg/dL (33%), associated with a rise in FENa. Differences between group I and group II using univariate analysis were: baseline serum creatinine (1.01 ± 0.23 mg/dL vs. 1.26 ± 0.19 mg/dL, p = 0.03), FENa (0.99 ± 0.8 vs. 2.2 ± 2.1, p = 0.04), furosemide dose during surgery normalized to body surface area (93.2 ± 23 mg/1.73 m² BSA vs. 135 ± 38 mg/1.73 m² BSA, p<0.001), and hemodilution index (17.3 ± 4.3% vs. 22.8 ± 3.2%, p<0.01). In the multiple regression model, baseline creatinemia and furosemide dose were associated to renal dysfunction.