Efficacy and safety of low molecular weight heparin in renal transplantation.

BACKGROUND: Deep venous thrombosis (DVT) is a common problem with potentially devastating results in patients undergoing major surgical procedures. Certain renal transplant recipients are particularly at risk for allograft loss as a consequence of renal vein and artery thrombosis. Over the past few years, low molecular weight heparin has been well established as an accepted modality of treatment and prophylaxis of DVT. The efficacy and safety of low molecular weight heparin in the prophylaxis of DVT following renal transplantation in adults has not previously been reported. METHODS: Dalteparin was administered to 120 adult renal transplant recipients postoperatively at the Oregon Health Sciences University. RESULTS: No patient developed allograft arterial or venous thrombosis. One patient developed subclavian vein thrombosis. No bleeding complications were encountered, and side effects were very minimal. CONCLUSION: Prophylaxis with dalteparin is an effective and safe modality for the prevention of thrombosis in adult patients undergoing renal transplantation.

A practical guide to the management of hypertension in renal transplant recipients.

Hypertension as well as hypotension can be harmful to a newly transplanted renal allograft. Elevated blood pressure is also a major risk factor for cardiovascular death, which is a frequent occurrence despite successful renal transplantation. Renal artery stenosis, immunosuppressive drugs, chronic rejection, retained native kidneys, and excessive extracellular fluid volume may all contribute to post-transplant hypertension. Antihypertensive agents are widely used in the management of post-transplant hypertension. Careful clinical judgement and knowledge of the pharmacology, pharmacodynamics, pharmacokinetics, adverse drug reaction profiles, potential contraindications, and drug-drug interactions of antihypertensive agents are important when therapy with antihypertensive drugs is initiated in renal transplant recipients. Since blood pressure elevation in any individual is determined by a large number of hormonal and neuronal systems, the effect of antihypertensive agents on the allograft should be considered a critical factor in the management of hypertension in renal transplant recipients. Most renal transplant recipients have other risk factors for premature cardiovascular death such as diabetes mellitus, hypercholesterolemia, insulin resistance, obesity, left ventricular hypertrophy and ischaemic heart disease. Initial antihypertensive therapy should be tailored individually according to the patient's risk factors. A realistic therapeutic goal for blood pressure management in the initial post-operative state is a systolic blood pressure <160 mm Hg and a diastolic blood pressure <90 mm Hg with lower pressure targets becoming applicable late post-transplantation.

Switching between cyclosporin formulations. What are the risks?

The introduction of cyclosporin, refinement in surgical techniques and improvement in allograft preservation have all led to an improvement in graft and ultimately patient survival. Cyclosporin is a lipophilic cyclic polypeptide produced by Trichoderma, a fungus isolated from Norwegian soil. Cyclosporin is a potent, selective and powerful immunosuppressive agent possessing a narrow therapeutic window. Substitution among different formulations of cyclosporin for economic reasons, without close monitoring of pharmacokinetics and pharmacodynamics, can induce undesirable toxic effects. A number of recent reports, largely anecdotal, of adverse drug reactions and acute cellular rejection after conversion from the standard formulation to the microemulsion formulation of cyclosporin have created uncertainty over the therapeutic equivalency of these agents. This leading article reviews the pharmacology, pharmacokinetics and adverse drug reactions of cyclosporin as well as the potential risks associated with switching between cyclosporin formulations in stable renal transplant recipients. Caution should be employed when switching between cyclosporin formulations. Since data are limited, long-term prospective studies are necessary to delineate the role of high peak concentrations obtained from the microemulsion formulation in relation to cyclosporin-induced chronic nephropathy. The significance of the reduction in pharmacokinetic variability with use of the microemulsion formulation in terms of graft and patient survival remains unclear.

Interaction between tacrolimus and nefazodone in a stable renal transplant recipient.

Tacrolimus (FK-506) is an important immunosuppressive agent most often given for maintenance immunosuppression to prevent acute cellular organ rejection. A 57-year-old woman with end-stage renal disease presumed secondary to chronic glomerulonephritis underwent a living related renal allograft transplantation. She tolerated the surgery well and was discharged on postoperative day 5. She was stabilized with prednisone, azathioprine, and tacrolimus. Two years after transplantation, nefazodone 50 mg twice/day orally was prescribed due to depression. After 1 week of nefazodone therapy the patient experienced headache, confusion, and "gray areas" in her vision, without abnormal ophthalmologic findings. Her serum creatinine was elevated to 2.2 mg/dl (baseline 1.5 mg/dl), and trough tacrolimus level was markedly elevated (> 30 ng/ml). Both tacrolimus and nefazodone are metabolized by the cytochrome P450 (CYP) 3A4 system. We suspect that nefazodone inhibits metabolism of tacrolimus. Coadministration of antidepressant agents such as nefazodone, or any other drug that inhibits the CYP3A4 isoenzyme subfamily, should be anticipated to interfere with tacrolimus metabolism. Monitoring blood concentrations of tacrolimus is vital, and appropriate dosage adjustments are required when the two drugs are administered concurrently to avoid serious interactions such as nephrotoxicity and neurotoxicity.

Use of basiliximab and daclizumab in kidney transplantation.

Kidney transplantation represents a major medical victory in patients with whom dialysis and medical therapy have failed. To increase survival rates and optimize the use of limited organs, both patient care and immunosuppression therapy must be improved. Reduction in rejection episodes or severity of rejection may ultimately improve long-term allograft survival. Traditional engineered monoclonal antibodies have been associated with severe cytokine release reactions and an increased risk of opportunistic infections. Basiliximab and daclizumab are chimeric and humanized monoclonal antibodies which inhibit thymus-dependent lymphocyte proliferation. Interleukin-2 also affects the proliferation of natural killer cells, macrophages and monocytes, bursa-equivalent lymphocytes, epidermal dendritic cells, and lymphokine-activated killer cells. Interleukin-2 receptor antagonists have been shown to reduce the incidence of acute rejection without increasing the incidence of opportunistic infections or malignancy. Further studies are needed to evaluate the overall effect of these agents on long-term patient and allograft survival.

Renal toxicity of protease inhibitors.

Introduction of several classes of antiviral agents for the treatment of immunodeficiency virus has led to increased survival and improved quality of life for patients with HIV infection. Protease inhibitors have become the mainstays of current therapy in patient with AIDS. Renal intolerance of indinavir is a rare but important complication in HIV positive patients. The renal function of patients receiving indinavir should be closely monitored. Benign and asymptomatic crystalluria occurs in 4-13% of HIV positive patients. Several cases of acute renal failure, renal atrophy and interstitial nephritis have also been reported. A hydration protocol consisting of one to two liters of fluid should be initiated three hours after each indinavir dose. If significant renal insufficiency persists, temporary indinavir withdrawal or switching to another protease inhibitor should be considered.

Kidney transplantation in children: a single center experience.

PURPOSE: We reviewed our most recent 10-year experience with kidney transplantation in children to determine the morbidity and mortality of the procedure, and to identify factors that affected outcome. MATERIALS AND METHODS: A total of 107 renal transplants were done in 95 children 1 to 17 years old (mean age 10.9) during the 10-year period ending January 1, 1997. The 4 most common causes of end stage renal disease were renal dysplasia, reflux nephropathy, obstructive uropathy and systemic immunological diseases. Cyclosporine based immunosuppression was used in all but 2 recipients. After April 1991 antilymphocyte antibody induction, coagulopathy screening, systemic anticoagulation and cytomegalovirus prophylaxis were incorporated into the protocols. The effects of kidney source, recipient gender, recipient age, preformed anti-HLA antibody level, preemptive renal transplantation, cytomegalovirus risk, antilymphocyte antibody induction therapy and date of renal transplantation on kidney graft survival were examined with the log rank test. RESULTS: The 1-year graft and patient survival rates were 91 and 99%, respectively. The most common causes of graft failure were rejection and recurrence of primary renal disease. The only factors that significantly (p < 0.05) influenced graft survival were antilymphocyte antibody induction immunosuppression and kidney transplantation after April 1991. Three urological complications required surgical correction. Medical morbidity included hypertension in 48.6% of the cases, short stature in 46.6% and obesity in 58.9%. CONCLUSIONS: Pediatric renal transplantation can be done with acceptable morbidity, a low rate of technical complications and low mortality. Hypertension, chronic rejection and abnormal body habitus continue to be problematic.