Effects of Renal Function on Plasma Digoxin Levels in Elderly Ambulant Patients in Domiciliary Practice

An investigation into the relations between the daily dose of digoxin, drug regimen, serum digoxin concentration, and creatinine and digoxin clearance was carried out in a group of elderly ambulant patients in domiciliary practice. Moderate to severe impairment of renal function was found both in patients taking digoxin and in elderly control subjects. Plasma digoxin levels were not related to blood urea concentrations or creatinine clearance. Digoxin clearance was less than creatinine clearance. Now that plasma digoxin levels can be measured relatively easily their estimation should become part of clinical practice.     

CANADIAN MEDICAL NEWS

Using the radioimmunoassay technique for measuring serum digoxin, it was found that patients who were given 0.25 mg. digoxin orally per day had a mean serum level of 0.83 ± 0.06 ng. per ml. In patients given 0.5 mg. daily the mean level was 1.30 ± 0.14 ng. A higher 24-hour urinary excretion of digoxin was associated with the higher serum levels in the latter group. Individuals who exhibited electrocardiographic evidence of digoxin toxicity had a mean serum level of 2.81 ± 0.21 ng. The majority of patients with high serum levels had evidence of impaired renal function, and it is in this clinical situation that knowledge of serum digoxin levels is likely to be most helpful in determining dose schedules.The method is specific, sensitive and reproducible. Repeated measurements on the same patient on maintenance therapy showed little variation. To obtain dependable serum levels blood should be drawn at least five hours after oral, and three hours after intravenous administration.     

Elevated levels of serum creatinine: recommendations for management and referral

BACKGROUND: The potential benefits of earlier referral to a nephrologist of patients with elevated levels of serum creatinine include identifying and treating reversible causes of renal failure, slowing the rate of decline associated with progressive renal insufficiency, managing the coexisting conditions associated with chronic renal failure and facilitating efficient entry into dialysis programs for all patients who might benefit. METHODS: A subcommittee of the Canadian Society of Nephrology, which included representatives from family practice and internal medicine, conducted a MEDLINE search for the period 1966 to 1998 using the key words referral and consultation, dialysis, hemodialysis, peritoneal dialysis, renal replacement therapy and kidney diseases. Where published evidence was lacking, conclusions were reached by consensus. GUIDELINES: Earlier referral to nephrologists of patients with elevated creatinine levels is expected to lead to better health care outcomes and lower costs for both the patients and the health care system. All patients with newly discovered renal insufficiency (as evidenced by serum creatinine elevated to a level above the upper limit of the normal range of that laboratory, adjusted for age and height in children) must undergo investigations to determine the potential reversibility of disease, to evaluate the prognosis and to optimize planning of care. All patients with an established, progressive increase in serum creatinine level should be followed with a nephrologist. Adequate preparation for dialysis or transplantation (or both) requires at least 12 months of relatively frequent contact with a renal care team. Nephrologists should provide consultation in a timely manner for any patient with an elevated serum creatinine level. In addition, they should provide advice about what aspects of the condition require particularly urgent or emergency assessment. SPONSORS: This clinical practice guideline has been endorsed by the Canadian Society of Nephrology and the College of Family Physicians of Canada. Meeting, teleconference and travel expenses of the Referral Guideline Subcommittee were covered by The Momentum Program, a collaboration between Baxter Corp. and Janssen-Ortho Inc. However, the authors are solely responsible for the editorial content of this article.     

Understanding the Risk Factors and Long-Term Consequences of Cisplatin-Associated Acute Kidney Injury: An Observational Cohort Study

Acute kidney injury (AKI) is a well-known complication of cisplatin-based chemotherapy; however, its impact on long-term patient survival is unclear. We sought to determine the incidence and risk factors for development of cisplatin-associated AKI and its impact on long-term renal function and patient survival. We identified 233 patients who received 629 cycles of high-dose cisplatin (99±9mg/m²) for treatment of head and neck cancer between 2005 and 2011. These subjects were reviewed for development of AKI. Cisplatin nephrotoxicity (CN) was defined as persistent rise in serum creatinine, with a concomitant decline in serum magnesium and potassium, in absence of use of nephrotoxic agents and not reversed with hydration. All patients were hydrated per protocol and none had baseline glomerular filtration rate (GFR) via CKD-EPI<60mL/min/1.73m². The patients were grouped based on development of AKI and were staged for levels of injury, per KDIGO-AKI definition. Renal function was assessed via serum creatinine and estimated glomerular filtration rate (eGFR) via CKD-EPI at baseline, 6- and 12-months. Patients with AKI were screened for the absence of nephrotoxic medication use and a temporal decline in serum potassium and magnesium levels. Logistic regression models were constructed to determine risk factors for cisplatin-associated AKI. Twelve-month renal function was compared among groups using ANOVA. Kaplan-Maier curves and Cox proportional hazard models were constructed to study its impact on patient survival. Of 233 patients, 158(68%) developed AKI; 77 (49%) developed stage I, 55 (35%) developed stage II, and 26 (16%) developed stage III AKI. Their serum potassium and magnesium levels correlated negatively with level of injury (p<0.05). African American race was a significant risk factor for cisplatin-associated AKI, OR 2.8 (95% CI 1.3 to 6.3) and 2.8 (95% CI 1.2 to 6.7) patients with stage III AKI had the lowest eGFR value at 12 months (p = 0.05) and long-term patient survival (HR 2.1; p<0.01) than patients with no or lower grades of AKI. Most common causes of death were recurrent cancer (44%) or secondary malignancy elsewhere (40%). Cisplatin-associated severe AKI occurs in 20% of the patients and has a negative impact on long-term renal function and patient survival. PEG tube placement may be protective and should be considered in high risk-patients.     

Fetal Endoxins and Complications of Pregnancy

Maternal endoxin (digoxinlike substance) is proposed as arising in the fetal area of the fetal adrenal cortex. Its function may be to sensitize the uterus for labor, much as does cortisol in the sheep fetus. Because endoxin is a sodium-potassium-adenosine triphosphatase inhibitor, however, it may also induce maternal vasoconstriction. On our service, normal pregnant women have detectable endoxin after 35 weeks with increasing amounts at term. Specimens of cord blood often have “digoxin” in the therapeutic range. We find that about 40% of women in premature labor and 65% of pregnant women with hypertension have elevated levels of serum endoxin. Postdate gravid women sometimes have very low endoxin levels. Pregnant women with complications and elevated digoxin (endoxin) levels could have specific antidigoxin therapy if endoxin proves to be a modulator of their symptoms. Digoxinlike substances are also sometimes elevated in ill nonpregnant persons, such as those with renal, liver, or heart failure, or hypertension.     

低血钾对原发性醛固酮增多症诊断的影响

目的：探讨低血钾对原发性醛固酮增多症（原醛）患者醛固酮水平的影响.方法：回顾性分析29例原醛患者,这些患者均接受血、尿醛固酮测定及立卧位速尿激发试验,并进行手术治疗.观察原醛患者血钾与醛固酮分泌的关系.结果：原醛患者低血钾时出现醛固酮正常的比例（8/16,50%）较正常血钾组高（2/13,15.4%）,P〈0.05.结论：低血钾可以抑制原醛患者尤其是特发性醛固酮增多症患者的醛固酮水平.     

Asymmetrical (ADMA) and symmetrical dimethylarginine (SDMA) as potential risk factors for cardiovascular and renal outcome in chronic kidney disease – possible candidates for paradoxical epidemiology?

Summary. Background: Asymmetrical dimethylarginine (ADMA) is an inhibitor of nitric-oxide synthase. It has been linked to atherosclerotic risk in the general population as well as in end-stage renal disease patients (ESRD), whereas symmetrical dimethylarginine (SDMA) is thought to be biological inactive. Prospective data concerning the role of both dimethylarginines are rare in patients with chronic kidney disease. Methods: 200 patients with chronic kidney disease (mean age 57.6 ± 13.0 years, 69 female, 131 male); 82 with chronic renal failure (CRF), 81 on maintenance haemodialysis (HD) and 37 renal transplant recipients (RTR) were prospectively followed for 24 months. ADMA and SDMA were measured by HPLC. The relation of plasma levels of ADMA and SDMA together with conventional risk factors for the cardiovascular and renal outcome was investigated with Cox proportional hazards model. Results: Mean serum levels of SDMA were significantly increased in all groups compared to the control group (P ≤ 0.0005), ADMA was increased only in HD and RTR (P ≤ 0.004). Forty-seven cardiovascular events (CVE) occurred during follow-up, 35 patients died, and 39 patients reached ESRD. Multivariate analysis showed diabetes (RR 3.072, P = 0.01), ESRD (RR 11.915, P < 0.0005), elevated CRP levels (RR 3.916, P < 0.0005) and surprisingly a lower ADMA level (RR 0.271, P = 0.008) as independent risk factors for CVE. Serum creatinine (RR 11.378, P = 0.001), haemoglobin (RR 0.710, P = 0.038 for an increment of 1 mmol/l), and SDMA levels (RR 1.633, P = 0.006, per 1 μmol/l increment) were predictors for the progression to ESRD. Conclusions: Data from a heterogeneous group of patients with chronic kidney disease provide evidence that conventional risk factors seem to play a more important role than elevated serum levels of ADMA or SDMA for cardiovascular events. Increasing serum SDMA concentration seems to play an additive role for the renal outcome besides serum creatinine and haemoglobin levels. Whether ADMA might possibly be a candidate for the phenomenon of “paradoxical epidemiology” in chronic kidney disease needs further investigation.     

Predicting compliance with a regimen of digoxin therapy in family practice.

The ability of family physicians to predict patients'' compliance with a regimen of digoxin therapy was studied by an analytic survey. Compliance was assessed by a pill count at a home visit and measurement of the serum digoxin level in a blood sample obtained at that visit. Of 74 patients 70% were found to be taking more than 80% of their pills and 86% had a therapeutic serum digoxin level. The 10 physicians were unable to predict compliance better than chance, even for the 58 patients they had known for 5 or more years. Physicians should be cautious in predicting compliance, and when they prescribe oral digoxin therapy they should monitor the patient''s compliance by means of the serum digoxin levels.     

心血管病患者住院治疗期间潜在的药物相互作用研究

目的:明确住院治疗的心脏病患者中潜在的药物-药物相互作用(drug-drug interaction,DDI),并对DDI相关危险因素进行评估。方法:选择2013年5月至2013年12月入院治疗的至少服用2种药物且入院不少于24小时的心脏病患者为研究对象,应用"标准药物相互作用数据库Micromedex-2(Thomson Reuters)×2.0"对这些患者可能发生的药物相互作用进行分析。结果:共入选150例患者,其中32例患者被确认出现了至少一种药物组合的DDI,发生率为21.3%;明确了48个有潜在危险因素的药物相互作用。阿托伐他汀/阿奇霉素(10.4%)、依那普利/二甲双胍(10.4%)、依那普利/氯化钾(10.4%)、阿托伐他汀/克拉霉素(8.3%)、呋塞米/庆大霉素(6.3%)是最常见的存在相互作用的药物组合,阿托伐他汀、依那普利、地高辛、呋塞米、氯吡格雷、华法林等药物经常参与药物相互作用。大多数药物的相互作用比较温和,但"用药种类增多、住院时间延长、存在合并症"等危险因素与潜在药物-药物相互作用(potential drug-drug interaction,p DDI)密切相关。结论:住院治疗的心脏病患者潜在DDI发生率较高,用药种类增多、住院时间延长、存在合并症均为其发生的危险因素。对那些存在明确危险因素的住院治疗的心脏病患者密切监测是十分必要的,医务人员要尽早发现和预防这些潜在的药物相互作用对人体健康造成的伤害。     

Plasma levels of cell-free apoptotic DNA ladders and gamma-glutamyltranspeptidase (GGT) in diabetic children

The plasma levels of apoptotic DNA ladders (i.e., apoptosemia) and gamma-glutamyltranspeptidase (GGT) in diabetic outpatients and rats were investigated. Apoptotic DNA ladders were detected in plasma from 26.8% of type 1 (T1) and 18.5% of type 2 (T2) diabetic children 1-20 years of age, 25.7% of hospitalized children and 35.7% of adult RA outpatients, but in only 3.5% of adult pre-op patients. Plasma from 7.7% of young streptozotocin-induced diabetic but not control rats contained apoptotic DNA ladders. Apoptosemia was detected more often in male T1 (31%) and T2 (30.8%) diabetic outpatients than in female T1 (20.8%) and T2 (15.4%) diabetic outpatients. GGT in apoptosemic plasma was significantly higher than in nonapoptosemic plasma from T1 (P = 0.001) but not T2 diabetic children. The highest amounts of apoptotic DNA were detected most often in diabetic children > or =14 years of age. In vitro study results suggest that cell-free apoptotic DNA ladders appear prior to an increase in GGT activity in serum from human blood incubated at 37 degrees C. The results suggest that 24.7% of plasma samples from diabetic children contained apoptotic DNA ladders, the incidence and amounts of apoptotic DNA ladders were higher in the older diabetic children, and GGT was elevated in apoptosemic T1 diabetic children (P = 0.01). The results indicate that "silent" apoptosemia occurs in T1 and T2 diabetic children and suggest elevated GGT in diabetic children could be due to release from apoptotic cells.     

Hypokalemia and alkalosis in adipsic hypernatremia are not associated with hyperaldosteronism

Idiopathic adipsic hypernatremia (AH) is a rare disorder associated with hypokalemia and alkalosis. Hypokalemic alkalosis has been presumed to be secondary to hyperaldosteronism. We evaluated plasma renin activity, serum aldosterone, serum and urine electrolytes in a 17-year-old patient with AH on several occasions. Despite evidence of mild dehydration, serum Na >160 and K <3.2, aldosterone levels were suppressed and plasma renin activity was not elevated. Urine Na and K were not conserved. We also examined electrolyte and hormone levels in previously reported cases of AH. Aldosterone levels were not increased in any of the cases when measured. Renin secretion was increased in 2 patients. Among the compiled cases serum K was inversely correlated with serum Na (r = -0.73, p < 0.002, n = 15). Hypokalemia and alkalosis occurring in AH are not associated with secondary hyperaldosteronism. Patients with AH may have chronic renal losses of potassium leading to hypokalemia and alkalosis.     

Serum digoxin in patients with thyroid disease.

Serum digoxin concentrations were measured by radioimmunoassay in 17 hyperthyroid and 16 hypothyroid patients after a seven-day course of oral digoxin. The significantly higher levels of serum digoxin in patients with hypothyroidism and lower levels in those with hyperthyroidism were closely related to the measured changes of glomerular filtration rate and digoxin serum half time in these two groups. Differences in serum digoxin concentration contribute to the altered sensitivity to digoxin shown by patients with thyroid disease.     

Alterations in blood and urine parameters in two florida manatees (Trichechus manatus latirostris) from simulated conditions of release following rehabilitation

In an effort to manage the existing population of the endangered Florida manatee (Trichechus manatus latirostris), as many individuals as possible are rehabilitated from illness or injury and released back into the waters of the state of Florida. It is not uncommon, however, for manatees recaptured for health assessment following release from rehabilitation to have elevated concentrations of serum creatinine. Although such elevated levels would be indicative of kidney failure in most other mammals, problems associated with renal function have not been evident in these recaptured manatees. To determine the possible cause(s) of the serum creatinine increase, two captive Florida manatees were manipulated to simulate many of the environmental and physical changes that occur during and shortly after release. Routine chemical analyses of serum and urine, complete blood counts, serum cortisol concentrations, and lymphocyte proliferation responses were measured. Serum creatinine concentrations increased significantly in response to decreased food intake and changes in food type. The increases differed depending on the salinity of the water in which the animals were maintained. It was found that significant changes in urinary creatinine and serum creatine kinase occurred as well, but serum cortisol concentrations were elevated only during simulated transport. Lymphocyte proliferation assays indicated that immune function was potentially impaired by extreme levels of dietary restriction and by changes in salinity. These results suggest that serum creatinine elevations and subsequent effects on the immune system might be minimized by adapting manatees undergoing rehabilitation to the diet and salinity they would encounter following release. Zoo Biol 22:103–120, 2003. © 2003 Wiley‐Liss, Inc.     

Mechanisms of digoxin-amiodarone interaction in the rat

Amiodarone and digoxin are often used in combination and clinical experience suggests that amiodarone may increase serum digoxin levels and toxicity. We have investigated the influence of amiodarone on digoxin pharmacokinetics and tissue distribution in the rat. Forty-nine rats were injected with 10 mg/kg amiodarone sc three times a day for 7 days, while 49 others were injected with saline only. On the eighth day, all the rats received 0.5 mg/kg digoxin ip; 4, 5, 6, 7, 8, 10, and 12 hr later, groups of 7 amiodarone-pretreated and control animals were sacrificed, and plasma, heart, liver, muscle, brain, and kidney digoxin concentrations measured by radioimmunoassay. Data were analyzed by two-way ANOVA, with group comparisons using the Waller-Duncan multiple comparison procedure. Digoxin levels were significantly higher in the plasma, heart, muscle, and kidney of the amiodarone-pretreated rats at most points of measurement (P less than 0.05) whereas liver digoxin levels were elevated at 8, 10, and 12 hr. Kidney/plasma, heart/plasma, muscle/plasma, and especially liver/plasma ratios in the control groups significantly exceeded the values found in the amiodarone-pretreated group at most time points. Concentrations of digoxin in brain were not changed. This suggests that the volume of distribution is significantly altered in the amiodarone-pretreated group. Amiodarone increases plasma digoxin levels in rats as it does in humans, but the mechanism is unclear.     

Serum IgG and Renal Transplantation

In 57 patients with renal allografts the prolonged administration of prednisolone ≥ 1 mg/kg/day and azathioprine ≥ 3 mg/kg/day caused a significant and persistent fall in serum IgG at all levels of creatinine clearance. The fall in IgG was more striking when creatinine clearance was below 25 ml/min. At lower doses of azathioprine and prednisolone serum IgG fell when the creatinine clearance was less than 35 ml/min, the degree of recovery towards normal being dependent on creatinine clearance and dosage. Post-transplant haemodialysis decreased the depression of IgG, and patients with immediately functioning grafts had minimal IgG depression. An inverse relation between IgG and IgM was observed in some patients. Severe infections and toxicity were associated with the greatest reduction in IgG; leucopenia and thrombocytopenia were not consistently reliable guides to toxicity. The deaths of four patients (7%) were associated with severe infections. Falls in IgG were not related to the rejection process. IgG measurement should be used as a guide to immunosuppression and toxicity in renal allograft patients.     

Use of β-Blockade and Hemoperfusion for Acute Theophylline Poisoning

Five adults were treated successfully for severe theophylline poisoning due to intentional overdosage. Clinical features included nausea, tremor, delirium, hypotension and cardiac arrhythmias, metabolic acidosis, hyperglycemia, hypokalemia and hypophosphatemia. No seizures or deaths occurred despite very high serum theophylline concentrations (between 96 and 194 μg per ml). Extreme elevations of plasma catecholamines were documented and are implicated in the toxicity. β-Blockade with intravenous administration of propranolol hydrochloride was the most effective therapy for theophylline-induced hypotension. All patients were treated with resin hemoperfusion, which resulted in significant clinical improvement and rapid lowering of the serum theophylline level.     

Lethal quercetin-digoxin interaction in pigs

Digoxin is a popular cardiac glycoside with very narrow therapeutic range. Quercetin is an ubiquitous antioxidant flavonoid. Digoxin is a substrate of P-glycoprotein (P-gp), a multi-drug efflux transporter, and quercetin was reported to be a modulator of P-gp. The aim of this study was to investigate the effect of quercetin on the absorption and disposition of digoxin in pigs. Pigs were orally given digoxin (0.02 mg/kg) with and without quercetin in crossover designs. The blood was collected via jugular vein and fluorescence polarization immunoassay was used to determine the serum concentration of digoxin. The pharmacokinetic parameters were calculated using WINNONLIN. The paired Student's t-test was used for statistical comparison. The coadministration of 50 mg/kg quercetin unexpectedly resulted in sudden death of two among three pigs within 30 min after digoxin administration. The coadministration of 40 mg/kg quercetin significantly elevated the C_max of digoxin by 413% and increased the AUC_0-t by 170%. The results indicated that a very serious pharmacokinetic interaction occurred between quercetin and digoxin. The concomitant administration of digoxin and quercetin or quercetin-containing herbs and dietary supplement should be avoided.     

Maintenance digoxin after an episode of heart failure: placebo-controlled trial in outpatients.

The need for maintenance digoxin treatment was assessed in a double-blind, variable-dose, crossover comparison with placebo. Forty-six outpatients who had been prescribed the drug for heart failure were studied; 33 were in sinus rhythm and the remainder in atrial fibrillation. Mean serum digoxin concentrations in those with sinus rhythm averaged 1-33 nmol/l, but a lower concentration, averaging 0-97 nmol/l, was accepted in those with atrial fibrillation as six of them developed bradycardia. Sixteen of the 46 patients deteriorated on placebo, and eight completely recovered when digoxin was reintroduced; in the remainder additional diuretics were required temporarily. Spirometric values deteriorated on changing to placebo whether or not the patient showed clinical evidence of recurrence of heart failure. In a separate study of nine patients who showed no clinical evidence of deterioration on placebo, reintroduction of digoxin caused a shortening of left ventricular ejection time, which persisted for at least a month. This suggests that the inotropic response to digoxin is sustained during maintenance treatment.     

Hyperkalemia Develops in Some Thyroidectomized Patients Undergoing Thyroid Hormone Withdrawal in Preparation for Radioactive Iodine Ablation for Thyroid Carcinoma

Objective: Hyponatremia is observed in hypothyroidism, but it is not known if hypo- or hyperkalemia is associated with hypothyroidism. To study these questions, we determined serum potassium (K⁺) levels in thyroidectomized patients undergoing levothyroxine withdrawal before radioactive iodine (RAI) therapy for thyroid carcinoma.Methods: We retrospectively studied the records of 108 patients who had undergone total thyroidectomy for thyroid carcinoma followed by levothyroxine withdrawal and then ablation with RAI at Nagasaki University Hospital from 2009–2013. Blood samples were analyzed for serum K⁺ concentrations when patients were euthyroid just before levothyroxine withdrawal and hypothyroid 21 days after levothyroxine withdrawal. We determined the proportion of patients who developed hyperkalemia (K⁺ ≥5 mEq/L) and hypokalemia (K⁺ ≤3.5 mEq/L).Results: Five (4.6%) patients developed hyperkalemia and 2 (1.9%) patients developed hypokalemia after levothyroxine withdrawal. The mean serum K⁺ level after levothyroxine withdrawal was significantly higher than before levothyroxine withdrawal (4.23 ± 0.50 mEq/L vs. 4.09 ± 0.34 mEq/L; P<.001). After levothyroxine withdrawal, serum K⁺ values were significantly correlated with age, serum sodium and creatinine levels, and the estimated glomerular filtration rate but not with serum free thyroxine or thyroid-stimulating hormone concentrations. The finding of an elevated serum K⁺ of >0.5 mEq/L after levothyroxine withdrawal was more prevalent with age >60 years (odds ratio [OR], 4.66; P = .026) and with the use of angiotensin-II receptor blockers or angiotensin-converting enzyme inhibitors (OR, 3.53; P = .033) in a multivariate analysis.Conclusion: Hyperkalemia develops in a small percentage of hypothyroid patients after thyroid hormone withdrawal, especially in patients over 60 years of age who are using antihypertensive agents that inhibit the reninangiotensin- aldosterone system.Abbreviations: ACE-I = angiotensin-converting enzyme inhibitor ARB = angiotensin-II receptor blocker Cr = creatinine eGFR = estimated glomerular filtration rate Eu-K⁺ = serum level of K⁺ in the euthyroid state Hypo-K⁺ = serum level of K⁺ in the hypothyroid state K⁺ = potassium Na⁺ = sodium ?K⁺ = Hypo-K⁺ value minus Eu-K⁺ value RAI = radioactive iodine TSH = thyroid-stimulating hormone     

肝移植术后急性肾功能衰竭的相关因素的临床分析

目的：探讨肝移植术后并发急性肾功能衰竭（ARF）的相关因素,为肝移植术后ARF的预防和治疗提供参考。方法：回顾性分析了2005年1月-2010年10月在我院行肝移植术的98例患者的临床资料,对术后并发ARF的相关因素进行分析。结果：98例行肝移植术后发生ARF13例,发生率为13．27％。单因素分析显示术前血尿素氮CBUN）、术前血清肌酐（Scr）、术前血清白蛋白（Alb）、手术时间、失血量与ARF的发生有关（P〈0．05）。多因素Logistic回归法分析表明,术前Ser和BUN是肝移植术后并发ARF的危险因素。结论：术前血BUN、血清Scr、血清Alb、手术时间和失血量是肝移植术后并发ARF主要因素,而术前Scr和BUN水平升高是肝移植术后并发ARF的危险因素。对上述因素加以重点评估和合理控制,可以控制肝移植术后ARF的发生。