L-arginine deficiency and supplementation in experimental acute renal failure and in human kidney transplantation

BACKGROUND: The "L-arginine paradox" refers to situations where L-arginine (L-Arg) supplementation stimulates nitric oxide (NO) synthesis, despite saturating intracellular concentrations. This paradox is frequently observed in acute renal failure (ARF). First, the effects of L-Arg on renal function of rats with ARF were studied. Based on the promising results from these initial studies, the second part of our study searched for a form of ARF in humans that could be studied easily under conditions with little variance and yet was linked with endothelial dysfunction. Thus, we investigated the effects of L-Arg supplementation immediately after kidney transplantation in 54 patients. METHODS: In uranyl nitrate-induced ARF in rats the effects of L-Arg and L-NNA (inhibitor of nitric oxide synthase; NOS) on glomerular filtration rate (GFR), renal plasma flow (RPF), blood pressure (BP) and NOx (NO2- +NO3-) excretion were examined. Tissue L-Arg levels, NOS activities, immunodetection of NOS and superoxide dismutase (SOD), activities of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase and xanthine oxidase, and nitrotyrosine immunoreactive protein (NT-IR) were determined and compared to sham operated animals. Secondly, in a randomized, double-blind study, the effects of L-Arg on GFR and RPF were investigated in 54 kidney transplant recipients, receiving IV L-Arg for three days. GFR and RPF were measured on days 1, 3, 5 and 10 by scintigraphy. RESULTS: In experimental ARF, decreased RPF and GFR were associated with reduced tissue L-Arg levels, endothelial NOS-III expression, NO formation and NOx excretion. Reduction in GFR, RPF and NOx excretion were reversed upon administration of exogenous L-Arg. There also was a loss of Cu,Zn-SOD, a key enzyme against oxidative stress, and an elevation of NT-IR, an indicator of nitrosative stress and suggested marker for pathological actions of NO. However, NT-IR was not dependent on de novo NO synthesis and not related to the functional effects of l-Arg administration. In kidney transplant recipients receiving organs with a short cold ischemia time (CIT) and from young donors, that is, those with a higher likelihood of a functional endothelium, early administration of L-Arg improved renal function. CONCLUSION: Both experimental and clinical data show that \L-Arg deficiency and endothelial dysfunction are pathomechanistically relevant in ARF. The data suggest a therapeutic potential for the administration of L-Arg in ARF and kidney transplantation, at least in patients receiving kidneys with shorter CIT and from younger donors.     

危重患者急性肾功能衰竭血液净化治疗的进展

在重症监护病房危重患者中,急性肾衰竭（ARF）是常见的严重并发症,发生率约5%,病死率高达50%～70%。近年来,危重ARF的血液净化治疗,尤其是在连续性肾脏替代治疗（CRRT）剂量、时机的研究取得了重要的进展,并出现了持续低效每日透析（sustained low-efficiency daily dialysis,SLEDD）等一些新的替代治疗模式。     

Fluvastatin in the treatment of dyslipidemia associated with chronic kidney failure and renal transplantation

Premature atherosclerotic coronary heart disease driven by multiple risk factors is a major cause of morbidity and mortality among the 6 million patients in the United States with chronic renal failure. Consensus is that kidney failure and renal transplantation patients should be treated aggressively for dyslipidemia. Major medical literature databases were searched for published information about fluvastatin, a HMG-CoA reductase inhibitor, used in patients with impaired renal function. This article characterizes the dyslipidemia observed in these clinical settings and reviews the clinical experience with fluvastatin.     

Prevention of acute renal failure after kidney transplantation

Summary The incidence of acute renal failure (ARF) after renal transplantation has always been about 50%. The most important factors for the development of ARF are the hemodynamic condition of the donor, the mode of preservation of the kidney, and the hemodynamic parameters of the recipient. Optimal hydration of the donor and the minimalization of the length of warm ischemia time decreased the incidence of ARF. Further improvement in the incidence of ARF could be achieved either by adding calcium antagonists to the preservation fluid or by using a new preservation fluid (Belzer solution). With moderate hydration of the recipient and the administration of mannitol just before clamp release, we also accomplished a decrease in ARF; however, neither moderate hydration nor mannitol alone could achieve this. By application of these methods, it is now possible after renal transplantation to achieve an incidence of ARF of <20%.     

连续性血液净化治疗心力衰竭Ⅳ级合并肾衰竭患者56例疗效观察

目的 观察和分析连续性血液净化在治疗重症心力衰竭合并肾衰竭中的作用和疗效.方法 应用连续性血液净化技术治疗2010年1月至2013年12月间我院收治的56例药物治疗效果不佳的重症心力衰竭合并肾衰竭的患者,并于治疗前后对患者心率、心脏指数、左室射血分数、心输出量、血肌酐（SCr）、尿素氮（BUN）、Na＋、K＋、Cl进行统计、分析和比较,观察患者心功能、血生化指标改善情况.结果 与治疗前相比,患者治疗后[心率（79.7±9.0）次/min、心脏指数（3.35±0.91）L/（min·m2）、左室射血分数（53.55±10.32）％、心输出量（4.47±0.35） L/min、SCr （392.00±86.32）μmol/L、BUN（11.2±4.5）mmol/L、K＋（4.4±0.5）mmol/L]均优于治疗前[心率（128.2±14.2）次/min,心脏指数（1.96±0.57） L/（min·m2）、左室射血分数（39.25±8.55）％、心输出量（3.08±0.54） L/min、SCr（903.00±106.10） μmol/L、BUN（20.5±9.4）mmol/L、K＋ （5.60±0.97） mmol/L差异具有统计学意义（P＜0.05）;而Na＋、Cl变化不大,无统计学差异（P＞0.05）.结论 连续性血液净化疗效确切,安全性高,是治疗重症心力衰竭合并肾衰竭的有效手段.     

Simultaneous heart and kidney transplantation for combined cardiac and renal failure

Simultaneous heart and kidney transplantation (SHKT) is feasible for combined cardiac and renal failure. Herein we reviewed our 10-year experience in SHKT. Six patients underwent SHKT from June 1995 to December 2004. Their ages ranged from 13 to 63 years old with a mean of 45.5 +/- 15.8 years. They were all men except one girl, who was the youngest (aged 13) who suffered from dilated cardiomyopathy with congestive heart failure and chronic renal failure due to systemic lupus erythematosus. Because of aggravating heart failure, she changed from hemodialysis to peritoneal dialysis. Because of intractable heart failure, she underwent SHKT from a 24-year-old female donor. All received hemodialysis before SHKT. The indications for heart transplantation included dilated cardiomyopathy (n = 3), ischemic cardiomyopathy (n = 1), cardiac allograft vasculopathy (n = 1), and cardiac allograft failure (n = 1). The immunosuppressive protocol and rejection surveillance were these employed for heart transplantation. No operative mortality was noted in this study. The 1-year and 5-year survival rates were the same, 83%. The 10-year survival rate was 55%. No cardiac or renal allograft rejection was noted. No renal allograft loss was noted. There were two late mortalities: the one, who underwent redo heart transplantation for coronary artery vasculopathy died of cardiac allograft failure 1 year after SHKT. The other patient died of massive ischemic necrosis of the intestine at 6 years after SHKT. Our experience showed that SHKT had good short- and long-term results without increasing immunosuppressive doses. End-stage failure of either the heart or the kidney did not preclude heart plus kidney transplantation.     

男性患者肾移植前后的阴茎勃起功能研究

目的　探讨男性肾功能衰竭患者肾移植前后的阴茎勃起功能,以提高肾移植患者的生存质量。方法　50例男性肾功能衰竭患者在肾移植前后填写国际勃起功能指数(IIEF)调查表,并同时测定性激素水平。结果　肾移植前阴茎勃起功能障碍(ED)发病率为84 %,肾移植后肾功能正常时降至54 %(P<0.05);术前血液透析时间在6个月以内者IIEF评分高于透析时间在6~24个月和超过24个月者;不论患者的年龄大小,肾移植术后IIEF评分均有不同程度的提高(P<0.05);肾移植后血清睾酮水平上升(P<0.05),雌二醇和催乳激素明显下降(P<0.05, P<0.01)。结论　肾移植能有效改善肾功能衰竭患者的阴茎勃起状况,受者术后的心理疏导有助于降低ED发病率。     

Prune belly syndrome: treatment of terminal renal failure by hemodialysis and renal transplantation.

The second case of successful renal transplantation in a patient with "prune belly" syndrome is reported. In spite of early aggressive surgical approach in the management of this disease terminal renal failure frequently ensues. Hemodialysis and renal transplantation have offered new possibilities of prolonging life in these patients. The success of renal transplantation depends on the anatomic and functional state of the lower urinary tract. Pretransplant urologic examination is extremely important for the evaluation of urinary tract abnormalities.     

不同血液净化方式对慢性肾功能衰竭的疗效分析

目的 比较不同血液净化方式对慢性肾功能衰竭（chronic renal failure,CRF）的疗效.方法 选取2005年至2011年期间本院收治的65例需要行血液净化治疗的CRF患者,随机分为3组,其中24例予血液透析联合血液灌流（Hemodialysis and hemoperfusion,HD＋ HP）、21例予血液透析（Hemodialysis,HD）、20例予腹膜透析（Peritoneal d（i）alysis,PD）,比较3组治疗前后各项临床指标的变化.结果 对比每组治疗前后的血尿素氮（BUN）、血肌酐（Cr）、收缩压（SBP）、舒张压（DBP）、血红蛋白（Hb）、二氧化碳结合力（CO2CP）,差异均有统计学意义（P＜0.05）;对比HD＋HP组治疗前后的β2-微球蛋白（β2-MG）差异有统计学意义（P＜0.05）,HD和PD两组组内对比治疗前后的β2-MG差异均无统计学意义（P＞0.05）.结论 HD＋ HP、HD和PD这三种血液净化方式治疗CRF均能有效改善患者的BUN、Cr、SBP、DBP、Hb、CO2 CP,而且HD＋ HP对于β2-MG的清除有着更加显著的效果.     

Heme biosynthesis and porphyrin studies in chronic renal failure patients following kidney transplantation

El-Far and Sobh were the first to describe abnormalities in porphyrin metabolism in Egyptian patients with chronic renal failure (CRF). Our results were confirmed by others. The present investigation aims to study and discuss the nature of those abnormalities and changes in porphyrin metabolism in CRF patients following kidney transplantation. Blood samples and urine were collected from patients (with and without polycythaemia) as well as from normal controls. The activity of heme enzymes such as ALA-S, ALA-D, URO-S, PBGase and URO-D were assayed. Total blood porphyrins as well as enzyme activities such as ALA-S and URO-S were found to be highly significantly increased in all patients, while URO-D activity remained within normal range. The observed elevated erythrocyte porphyrins may be mainly due to increased activity of ALA-S, the rate-limiting enzyme in heme synthesis. The present study is the first of its kind which clearly demonstrates that successful kidney transplantation does not correct or rectify the abnormalities in porphyrin metabolism.     

The bioartificial kidney in the treatment of acute renal failure

The application of cell therapy to the successful substitution process of hemofiltration may improve the poor prognosis of patients with acute renal failure (ARF) in the intensive care unit. An extracorporeal bioartificial kidney consisting of a conventional hemofilter followed in series with a renal tubule assist device (RAD) has been developed. The RAD is a hemofiltration cartridge containing 109 human renal tubule cells grown as monolayers along the inner surface of the hollow fibers. The fibers provide a porous scaffold that is immunoprotective. The ultrafiltrate from the hemofilter is delivered to the luminal compartment of the RAD, and the postfiltered blood is delivered to the extracapillary space of the RAD. The RAD has been shown to possess multiple differentiated transport, metabolic, and endocrinologic activities of renal epithelium. These activities have been demonstrated to occur when the RAD is placed in the extracorporeal circuit of the bioartificial kidney in uremic animals. This approach may improve the current therapies used to treat patients with ARF because of the RAD's ability to restore lost metabolic renal function and cytokine balance in these desperately ill patients. In this regard, the RAD was able to ameliorate endotoxin and bacteremic shock in uremic animals by altering cytokine levels, improve mean arterial blood pressure, and maintain better cardiac output. With these supportive preclinical data, an FDA-approved phase I/II clinical trial has been initiated and early results are encouraging.     

肝移植相关性肾功能衰竭的防治

目的 总结肝移植相关性肾功能衰竭(肾衰)的防治经验。方法 回顾性分析36例术后早期肝移植相关性肾衰防治方法的改进及效果。结果 36例肝移植受者中，死亡10例，死亡率为27．78％。术后并发症：肺部感染22例；多器官功能衰竭11例；成人呼吸窘迫综合征(ARDS)14例；腹腔内出血4例；胆漏1例。术后2例存活超过3年，4例存活超过2年，9例存活超过1年。结论 采用背驮式肝移植；改进连续性肾替代治疗(CRRT)的使用方法；术后早期使用赛尼哌；减少或完全不用钙调素抑制剂；是提高肝移植相关性肾衰治疗成功率的关键。     

肾移植中供肾血管变异的处理

目的提高血管变异的供肾的临床应用价值。方法根据具体情况，将血管变异的供肾进行合并、修整、重建等，使供肾安全、有效的移植给受者。结果78只供肾动脉变异(包括23只供肾静脉变异)经处理后，77只供肾良好。供肾移植后数分钟内有尿排出，2周内肾功能恢复正常，1年后随访无并发症。仅有1例因肾静脉回流障碍，被迫切除移植肾。结论供肾血管变异只要正确处理，移植后可获得良好效果。     

Simultaneous heart and kidney transplantation in patients with end-stage heart and renal failure.

Combined simultaneous organ transplantation has become more common as selection criteria for transplantation have broadened. Broadening selection criteria is secondary to improved immunosuppression and surgical techniques. The kidney is the most common extrathoracic organ to be simultaneously transplanted with the heart. A series of 13 patients suffering from both end-stage heart and renal failure underwent 14 simultaneous heart and kidney transplantations at Temple University Hospital between 1990 and 1999. This is the largest series reported from a single center. Three patients died during the initial hospitalization for an in-hospital mortality of 21%. Of 10 patients who left the hospital, 1-year survival was 100% and 2-year survival 75%. One patient required retransplant for rejection within the first year. Overall mortality at 1 and 2 years was 25 and 41%, respectively. Four out of nine (44%) patients greater than 5 years post-transplant were alive. Of the 10 patients who left the hospital, 66% were alive at 5 years. One patient succumbed to primary nonfunction of the cardiac allograft, while the four other deaths were secondary to bacterial or fungal sepsis. The patient's racial backgrounds were equally divided between African-American and white. These results are similar to those reported in a United Network of Organ Sharing Database (UNOS) registry analysis of 84 simultaneous heart and kidney transplants that found 1- and 2-year survival to be 76 and 67%, respectively. Simultaneous heart and kidney transplantation continues to be a viable option for patients suffering from failure of these two organ systems, although the results do not match those of heart transplant alone.