Luis Arrazola

Pharmacokinetics of FK506 After Intravenous and Oral Administration in Patients Awaiting Renal Transplantation

The authors examined the safety and pharmacokinetics of FK506, a new hepatically metabolized immunosuppressant, after single‐dose intravenous (IV) infusion (20 μg · kg−1 · 4 hours−1) and oral (80 μg/kg) administration in six nondialysis patients, aged 27 to 53 years, with chronic renal failure awaiting transplantation. A two‐period, randomized, crossover study protocol was used with blood samples drawn for 72 hours after each dose and a washout period of 4 days. Whole‐blood FK506 levels were determined using a standard, two‐step, nonspecific enzyme immunoassay. There were no significant changes in vital signs, EKG, or complete laboratory test battery for any patient during the entire study period. No side effects were noted after IV or oral FK506 dosing. Mean ± SD distribution half life was 0.9 ± 0.2 hours, elimination half life (t1/2β) 33 ± 8 hours, total body clearance (CL) 2.4 ± 1.1 L/hour, and bioavailability 14 ± 12%. There was no significant correlation between serum creatinine (Cr) and CL (r = 0.36) or between Cr and t1/2β (r = −0.30). It was found that FK506 is incompletely and erratically absorbed after oral administration and is rapidly distributed outside the blood compartment after IV dosing. An extended sampling period seems necessary to accurately characterize the slow elimination phase of FK506.

Kidney transplantation in young children: should there be a minimum age ?

Abstract. The optimal age for transplantation in children with end-stage renal disease remains controversial. Many centers have adopted a policy of waiting until such children reach a certain minimum age or weight, maintaining them on chronic dialysis until then. Their policy is based on historical data showing inferior graft survival in very young children. We feel that with proper donor selection and recipient care, comparable results can be achieved in very young age groups. We herein present our results with kidney transplantation in children <1 year old. Between 1 January 1984 and 31 December 1999, we performed 321 kidney transplants in children ≤13 years at the University of Minnesota. We analyzed our results in three age groups: <1 year (n=30), 1 through 4 years (n=122), and 5 through 13 years (n=169). We found no significant differences in patient or graft survival rates between the three groups. Almost all our infant (<1 year) recipients underwent primary transplants from living donors (LDs). However, even when we compared results only of primary LD transplants between the three groups, we found no significant differences. To date, all our infant recipients are alive and well, 24 (80%) with a functioning original graft. Causes of the 6 graft losses were chronic rejection (n=3), vascular thrombosis (n=2), and recurrent disease (n=1). Infants had significantly lower incidences of acute and chronic rejection compared with older recipients, but a tendency to higher incidences of delayed graft function and vascular thrombosis. Infants had significant increases in weight post transplant: the mean standard deviation score rose from –2.8 pre transplant to –0.2 by age 5 years and to +1.8 by age 10 years. The improvement in height was less marked: the mean standard deviation rose from –3.2 pre transplant to –1.6 by age 5 years and to –1.4 by age 10 years. Kidney transplant results in very young children can be comparable to those in older children. There need be no minimum age for performing a kidney transplant. The timing of the transplant should not be based on age or size alone.

May-Thurner syndrome in renal transplantation.

renal insufficiency. Intraarticular corticosteroids may be considered in patients in whom other drugs may be dangerous and one or few joints are involved. Parenteral pulse corticosteroids may be considered otherwise. Correction of serum magnesium levels has been reported to associate with reduction of the number of pseudogout attacks (5, 6) and should be considered in patients with hypomagnesemia. Patients on tacrolimus therapy who present with acute arthritis should be investigated for serum magnesium levels, radiological chondrocalcinosis, and careful search of CPPD crystals in synovial fluid samples. Additionally, cultures of synovial fluid and also of blood and the site of any potential source of infection should not be neglected for cultures despite finding crystals in synovial fluid samples, as septic arthritis may also occasionally complicate crystalline arthritis. Prevention of factors that could lead to CPPD crystal deposition, such as hypomagnesemia, should be considered, and proper correction of magnesium deficiency can prevent further pseudogout attacks in magnesium-deficient patients (1, 6).

An absent inferior vena cava in a pediatric renal transplant recipient

The patient, a 13-month-old female, was born with autosomal recessive polycystic kidney disease (ARPKD) and pulmonary hypoplasia. She had been on hemodialysis for the previous 6 months because of malignant hypertension. Subsequently, she required bilateral nephrectomies. In addition, she had already developed hepatic fibrosis with portal hypertension, esophageal varices, and persistent thrombocytopenia as expected in most patients with AR-PKD (1). She was evaluated for a combined cadaveric liver and kidney transplant. However, since her synthetic liver function was adequate and her portal hypertension stable, she was then considered for a living related kidney transplant. Her mother was found to be a suitable donor, having a 3-antigen HLA match. The patient underwent a living related kidney transplant on 17 September 1998. The operation proceeded normally until the distal aorta and proximal common iliac vessels were exposed; it then became evident that the inferior vena cava was absent (Figs. 1 and 2). After extensive dissection of the retroperitoneum, a small vessel (about 3 mm in diameter) was identified that appeared to be a branch of the left common iliac vein. With no other options for venous reconstruction, we used this small branch in an end-to-side anastomosis with the donor renal vein. The renal artery was then connected in an end-to-side fashion to the recipient’s aorta. The ureter was anastomosed to the bladder using the Leadbetter-Politano technique. Induction immunosuppression included methylprednisolone (2 mg/kg), Zenapax (daclizumab, the study drug for a research protocol; 1 mg/kg), and azathioprine (1.25 mg/kg), followed by cyclosporine on postoperative day 3. Postoperatively, her graft function progressively improved. Venous duplex studies confirmed the patency of the anastomosis. Her postoperative course was somewhat prolonged secondary to pulmonary care and nutritional requirements. She was discharged home on postoperative day 26 with a creatinine level of 0.2 mg/dL.