Effect of a new antithrombotic agent (defibrotide) in acute renal failure due to thrombotic microangiopathy

8 patients with thrombotic microangiopathy were treated with a new antithrombotic agent, defibrotide. This drug displays considerable fibrinolytic and antithrombotic activity, and induces generation and release of a prostacyclin-like substance from vascular tissue. At admission all patients presented severe renal involvement and coagulation abnormalities. Neurological manifestations were present in 6. Defibrotide administration was followed by recovery of renal function in 6, disappearance of neurological symptoms and coagulation abnormalities in all patients. The use of defibrotide was not associated with side effects. On the basis of the results obtained in these patients, we suggest that defibrotide might be considered as a valuable drug in the management of patients with thrombotic microangiopathy.     

The effect of graft function on FK506 plasma levels, dosages, and renal function, with particular reference to the liver.

Plasma FK506 was studied in 49 liver, 13 heart, 3 double-lung or heart-lung, and 21 kidney recipients. The levels were correlated with the drug doses used, kidney function, and liver function. In all varieties of recipients, there was an early rise in the FK506 plasma levels that occurred at the time of intravenous administration of the drug. At the same time or shortly after, there were increases in serum creatinine that were transitory except in liver recipients with continuing suboptimal graft function. The quality of hepatic function dominated all aspects of FK506 management in the liver recipients. Those who received well-functioning grafts could be given about the same drug doses as recipients of kidneys and the thoracic organs. Liver recipients with defective grafts had astronomical rises in plasma FK506, a high incidence of renal failure, and probably increased neurotoxicity. In kidney transplant recipients, the FK506 plasma levels and doses were essentially the same in patients with prompt versus delayed renal function. These studies have highlighted the necessity, first, of close pharmacologic monitoring of patients who are given FK506 in the presence of abnormal liver function, and second, of using smaller intravenous induction doses than in past practice.     

Cyclosporine in the treatment of azathioprine-induced red cell aplasia following renal transplantation

Azathioprine, a well-known immunosuppressive agent, is used extensively in renal transplantation. There have been several case reports of pure red cell aplasia induced by this drug following a successful kidney transplant. Previous management of azathioprine-induced red cell aplasia included reduction of azathioprine dose, or treatment with cyclophosphamide. We propose the substitution of cyclosporine for azathioprine, in this clinical setting. Not only does cyclosporine allow recovery of bone marrow function, but it maintains a level of immunosuppression which stabilizes renal function in the post-transplant patient.     

The medical management of renal artery stenosis in transplant recipients.

The investigation, management and clinical course of 12 patients developing stenosis of the renal artery following transplantation are described. The possible aetiology of the three arteriographic patterns of stenosis is discussed. Surgical correction of graft arterial stenosis is difficult and may lead to graft loss, whereas the outcome with antihypertensive drug treatment with or without anticoagulants is good. Surgery should only be contemplated if medical treatment is failing or if renal function is deteriorating.     

Study of renal function matching between Banna Minipig Inbred line and human

Pigs have been thought to be ideal candidates for xenotransplant donors. However besides the immunological barrier, physiological and pharmacokinetic comparabilities of kidney function between donor animals and humans are important factors for successful xenotransplantation. As a unique large inbred animal, Banna Minipig Inbred (BMI) has been reported to be a potential large animal suitable for xenotransplantation. However, its physical and pharmacokinetic compatibilities with humans have not been documented. The purpose of this investigation was to measure renal routine function, glomerular filtration rate (GFR), renal blood flow (ERPF), and drug metabolism to evaluate comparability to humans. The results suggested that the renal function of BMI was similar to that of humans to eliminate nonprotein nitrogenous end products of metabolism. Pharmacokinetics of p-aminohippurate (PAH) and inulin--the most widely used methods to assess ERPF and GFR--showed that BMI showed lower values than humans for GFR, but similar function to humans in ERPF. The pharmacokinetics of cefazolin; a widely used model drug to study kidney drug metabolizing capacity, showed greater overall renal drug elimination of BMI than of humans. These results suggested that BMI did show comparable data to human renal function.     

Chronic kidney disease

Chronic kidney disease (CKD) is a common disorder as currently defined. Patients with CKD face two major hazards: cardiovascular disease and – in a minority – progression to end-stage renal disease (ESRD). Advanced CKD also causes numerous metabolic and other complications. The management of CKD involves excluding acute kidney injury, diagnosing the cause of CKD, slowing progression and detecting and treating complications. Surgeons seeing patients with CKD should aim to optimize fluid balance in the perioperative period, avoid nephrotoxic agents and ensure drug doses are appropriate for the level of renal function. Nephrological input should be sought early if required.     

Use of antiepileptic drugs in patients with kidney disease

The number of medications used to treat different types of seizures has increased over the last 10-15 years. Most of the newer antiepileptic drugs (AEDs) are likely to be unfamiliar to many nephrologists. For both the older and newer AEDs, basic pharmacokinetic information, recommendations for drug dosing in patients with reduced kidney function or who are on dialysis, and adverse renal and fluid-electrolyte effects are reviewed. Newer AEDs are less likely to have significant drug-drug interactions than older agents, but are more likely to need dosage adjustment in patients with reduced kidney function. The most common renal toxicities of these drugs include metabolic acidosis, hyponatremia, and nephrolithiasis; interstitial nephritis and other adverse effects are less common. Little is known about the clearance of most of the newer AEDs with high-efficiency hemodialyzers or with peritoneal dialysis. Monitoring of drug levels when available, careful clinical assessment of patients taking AEDs, and close collaboration with neurologists is essential to the management of patients taking AEDs.     

临床肝肾移植三例体会

目的　探讨肝肾序贯移植和同期联合移植的手术难点及围手术期处理要点。方法　对2例肾移植术后发生药物性肝损害的病例实施肝移植 ,并对 1例巨大多囊肝、多囊肾的病例实施肝肾联合移植。结果　 2例肾移植术后实施肝移植的病例 ,其中 1例因术后肾功能衰竭导致多器官功能衰竭死亡 ;另 1例术后肝、肾功能良好 ,现已存活 1年。肝肾联合移植病例术中采用肝后腔静脉直接阻断法 ,使重达 10kg的巨大病肝得以顺利切除 ,并采用腔静脉成型术完成改良背驮式肝移植。术后免疫方案采用人源化单克隆抗体达利珠单抗免疫诱导下的以FK5 0 6、霉酚酸酯 (MMF)和激素的三联用药 ,肝、肾功能恢复良好 ,现为术后 6个月。结论　序贯性肝肾移植在术前应该准确评估移植肾功能 ,如果移植肾功能不良 ,应果断选择实施肝肾联合移植。肝后下腔静脉直接阻断法在实施巨大病肝切除时具有较大优势。肝肾联合移植术中及术后建议采用达利珠单抗免疫诱导下的免疫三联用药。     

Pharmacology and pharmacotherapy of cardiovascular drugs in patients with chronic renal disease

Cardiovascular disease is a common comorbidity and a major cause of mortality in patients with chronic renal disease. Drug regimens in patients with cardiovascular disease are frequently complex and can be significantly affected by alterations in renal function. In addition, several cardiovascular drugs directly affect renal function and the management of patients with renal disease. This article reviews the impact of renal disease on the pharmacokinetics of cardiovascular drugs and identifies clinically important interactions between these and other drugs commonly used in the management of chronic renal disease. Several classes of cardiovascular drugs are also discussed in relationship to their differential effects on the management and progression of renal disease.     

The management of abdominal aortic aneurysms in patients with concurrent renal impairment.

INTRODUCTION: Patients with concurrent renal impairment and abdominal aortic aneurysms present a significant challenge in terms of pre-operative, intra-operative and post-operative management. This aim of this review was to determine the risks of surgery in this patient group and determine whether any clear management strategies exist to enhance their clinical management. METHODS: Systematic review of published literature giving details of the outcome of open or endovascular abdominal aortic aneurysm repair in patients with pre-operative renal impairment. Papers concerning the management of post-operative acute renal failure in patients with normal pre-operative renal function has not been included. RESULTS: There is little data regarding patients with end-stage renal failure and AAA although these patients appear to have a high peri-operative mortality rate. In contrast, those with renal impairment do not have a significantly higher mortality rate than those with normal renal function, rather they have a higher risk of complications associated with surgery and may require more intensive post-operative organ system support than normal patients. Many have a transient deterioration in renal function in the immediate peri-operative period that will resolve. In the case of patients with ruptured AAA, it is not clear whether pre-operative renal impairment affects mortality.     

Perioperative management of patients with chronic kidney disease or ESRD

The perioperative management of patients with chronic kidney disease (CKD) or dialysis-dependent end-stage renal disease (ESRD) is complicated by both the underlying renal dysfunction, with associated disturbances of fluid and electrolyte homeostasis and altered drug clearance, and the presence of associated co-morbid conditions, including diabetes mellitus, chronic hypertension and cardiovascular and cerebrovascular disease. The impact of CKD on fluid and electrolyte management, haematological and cardiovascular complications and drug management in the perioperative period are reviewed. Special issues related to the management of haemodialysis and peritoneal dialysis patients in the perioperative period are also reviewed.     

Determinants for the prognosis of acute renal disorders that developed during or after treatment with edaravone

Background  Edaravone, a drug for treating acute ischemic stroke, has been reported to provoke acute renal disorders. In the previous study, the author evaluated the role of edaravone in the development of renal disorders in 207 patients reported as having developed them in the post-marketing survey of the drug. The overall recovery rate of renal function in the survey was 43%. Risk factors that affect the recovery rate of renal function and mortality remain to be clarified. Methods  The recovery rate of renal function and mortality rate were examined according to the extent of edaravone involvement in renal disorder onset, which was defined by the concurrence of other risk factors for renal disorders, in previously reported 207 patients. Risk factors for the nonrecovery of renal function and death were determined by using a stepwise logistic regression analysis. Results  The recovery rate of renal function was low and mortality rate was high in the group where the above extent of edaravone involvement was slight. The above analysis showed that risk factors for the nonrecovery of renal function were the complication of severe infection and the implementation of blood purification, and that risk factors for death were advanced age (≥80 years) and the complication of severe infection. Conclusions  The nonrecovery rate of renal function and mortality rate were high in the cases of patients that were complicated with factors that affected renal function other than edaravone. The complication of severe infection was a risk factor for the nonrecovery of renal function and for death.     

Rapid onset intratubular calcification following renal transplantation requiring urgent parathyroidectomy

BACKGROUND: Secondary hyperparathyroidism is a common complication of end-stage renal disease often requiring parathyroidectomy. Renal transplant with the restoration of normal renal function often allows resolution of hyperparathyroidism, avoiding the need for parathyroid surgery. However, a proportion of patients with hyperparathyroidism become overtly hypercalcemic after renal transplantation which poses management dilemmas between medical and surgical treatment. CASE: We present the case of a 48-yearold man with end-stage renal failure known to have secondary hyperparathyroidism who received a living related renal transplant. Postoperatively he developed prompt hypercalcemia, polyuria, polydipsia and rapid onset intratubular calcification, leading to acute tubular necrosis diagnosed on renal biopsy on Day 7 post transplantation. He underwent surgical parathyroidectomy with resolution of his hypercalcemia and improved renal transplant function. DISCUSSION: This case emphasizes the need for good management of secondary hyperparathyroidism together with close surveillance of PTH in patients awaiting renal transplantation. With good renal transplant function hyperparathyroidism usually resolves. Posttransplant surgical parathyroidectomy should be reserved for severe progressive end organ damage.     

Neonatal intervention for severe antenatal pyelocaliectasis

The postnatal management of the antenatally detected ureteropelvic junction obstruction relies on several factors, including the degree of hydronephrosis detected postnatally, the renogram washout curve, and the degree of renal function. It is imperative for the urologist to review all renal scans because of the inherent pitfalls in performing and interpreting these studies. A select population demonstrating severe pyelocaliectasis and poor function exists in which an intraoperative renal biopsy may be a better predictor of future renal function when compared with the preoperative renal scan. We present a patient with poor renal function that normalized with early surgical intervention.     

Effect of Perioperative Administration of a Drug Regimen on the Primary Function of Human Renal Allografts

Delayed graft function (DGF) has one of the greatest effects on short- and long-term outcomes of cadaveric renal allografts. Ischemia reperfusion injury in the context of cold ischemia time and acute calcineurin inhibitor (CNI) nephrotoxicity is a major factor predisposing to DGF. A drug regimen consisting of prostaglandin E₁ (PGE₁) furosemide and dopamine has been used to reduce DGF after kidney transplantation. Prostaglandin E₁ has multiple anti-ischemic and tissue-protective abilities, furosemide improves diuresis, and dopamine augments renal blood flow and urinary volume. To evaluate a potential positive effect of this drug regimen on the primary function of cadaveric renal allografts, we performed a retrospective single-center study that compared 100 patients who received this regimen with a control group. The results showed no significant improvement in renal function. In contrast, plasma levels of creatinine and urea were increased in the drug regimen group. Thus, the effectiveness of PGE₁ in combination with high-dose furosemide and dopamine in diminishing DGF was not demonstrated in this trial.     

Renal function one year after switching from Sandimmun to Neoral

BACKGROUND: The replacement of Sandimmun by Neoral in 1995 was thought to cause subsequent renal function deterioration due to the better bioavailability of the new drug. We prospectively analyzed the effect of a dose-to-dose drug replacement on renal function over 12 months. METHODS AND RESULTS: The renal function of 47 consecutive heart transplanted patients was prospectively evaluated before (T0), at 1 (T1), 3 (T3), and 12 (T12) months after drug replacement. Mean serum creatinine was not significantly different at T0 and T12 (142 +/- 55 and 154 +/- 60 micromol/L, p = 0.1). We were able to reduce cyclosporine total and weight-indexed doses by, respectively, 11% and 14% between T0 and T12 (274 +/- 86 to 244 +/- 72 mg/d, p = 0.0003; and 3.7 +/- 1.4 to 3.2 +/- 1.2 mg/kg/d, respectively, p = 0.0005). CONCLUSIONS: This study demonstrates that the dose-to-dose replacement of Sandimmun by Neoral is feasible, with no direct influence on renal function over a 1-yr follow-up.     

Impacts of dosing and drug withdrawal period on tacrolimus-based triple therapy in a non-human primate renal transplantation model

Non-human primate (NHP) renal transplantation models are widely used vivo models for researching new immunosuppressive therapies including allograft tolerance strategies. To enroll animals into a tolerance study, an immunosuppressive regimen that efficiently establishes stable renal function in NHPs is needed. Here, we assessed the effect of triple therapy comprising 2.0 mg/kg tacrolimus, mycophenolate mofetil and a steroid and its success rate for achieving stable renal function. In addition, to predict the pathophysiological consequences of withdrawing immunosuppressants, an indispensable process after induction of tolerance, we also assessed changes in the stable renal state maintained by triple therapy after drug withdrawal. Six cynomolgus monkeys were used. The median survival time was >176 days over the dosing period and 45 days after drug withdrawal. The triple therapy successfully induced stable graft function without calcineurin inhibitor nephrotoxicity in three of six recipients, although adopting trough-dependent tacrolimus dose adjustment rather than a preset dose regimen could improve on the present strategy. Further, drug withdrawal led to deterioration of renal function, de novo donor specific antibody production and increased the memory/naïve T cell ratio within two weeks post drug withdrawal. We expect that these findings contribute to establish one of the choices for animal model for evaluating future tolerance therapy for renal transplantation.     

Mycophenolate mofetil restores renal function and spares steroids during idiopathic nephrotic syndrome in children. A cohort study

Renal function evolution during idiopathic nephrotic syndrome depends on treatment toxicity. Cyclosporin is effective as a steroid-sparing agent but patients are dependant on this drug, which can lead to renal toxicity. Mycophenolate mofetil, a widely used drug in organ transplantation, has short-term beneficial effects in glomerular diseases, including idiopathic nephrotic syndrome. Little is known about mycophenolate mofetil in children and long-term evolution. We analysed a cohort of 12 children with steroid-dependant nephrotic syndrome due to minimal change disease in remission with cyclosporine therapy. They were switched to mycophenolate mofetil, when renal toxicity was diagnosed. We evaluated the number of relapses, tolerance of this new treatment, renal function and body mass index under mycophenolate. After a follow-up of 31.25 months, mycophenolate mofetil alone was effective in preventing relapses in eight patients, without side effects. Renal function significantly improved and the final body mass index decreased. Three patients relapsed on discontinuation of mycophenolate mofetil. The results suggest that mycophenolate mofetil is effective and safe in preventing relapses in steroid-dependant nephrotic syndrome. Furthermore, switching from cyclosporine to mycophenolate mofetil restores renal function. Therefore, mycophenolate mofetil might be considered as an alternative to cyclosporine, to preserve renal function and spare steroids during idiopathic nephrotic syndrome in children.     

Chronic irreversible nephrotoxicity from cyclosporin A

A 43-year-old woman developed progressive renal insufficiency while receiving cyclosporin A after live donor kidney transplantation. Despite the discontinuation of this drug and substitution with azathioprine, the renal function continued to deteriorate leading to eventual graft loss. The other causes of chronic renal failure such as allograft rejection, recurrent or 'de novo' glomerulonephritis or obstructive uropathy were not evident. There is a high frequency of acute reversible nephrotoxicity from cyclosporin A, but this patient's clinical course suggests that chronic irreversible renal failure can also occur in patients receiving this drug.