Mark A. Hardy

Multicenter, randomized study of the use of everolimus with tacrolimus after renal transplantation demonstrates its effectiveness

Background. Clinical data are lacking concerning concomitant administration of everolimus and tacrolimus in renal transplant recipients. Methods. In a prospective, multicenter, open-label, exploratory, randomized, 6-month study, 92 de novo renal transplant patients received everolimus, steroids, and basiliximab with low or standard tacrolimus exposure. The primary objective was to compare renal function at 6 months after transplant. Results. Mean 6-month serum creatinine (primary safety variable) was 112±31 &mgr;mol/L (1.26±0.35 mg/dL) and 127±50 &mgr;mol/L (1.44±0.57 mg/dL) in the low and standard tacrolimus groups, respectively, (n.s.); mean estimated GFR (Nankivell) was 75.3±16.6 mL/min and 72.5±15.2 mL/min (n.s.). Biopsy-proven acute rejection occurred in 13 patients: seven (14%) in the low tacrolimus group and six (14%) in the standard tacrolimus group, n.s. One graft was lost in the standard tacrolimus group. No patients died. Conclusions. Tacrolimus exposure reduction in the presence of everolimus, steroids and basiliximab induction results in good efficacy in de novo renal transplant recipients with very well-preserved renal function. Additional studies are warranted because between-group comparisons were limited by the relatively small differences in tacrolimus exposure in the 2 arms; trough levels were toward the upper end of the low-exposure ranges and toward the bottom of the standard-exposure ranges.

Diagnosis and Management of Cardiovascular Disease in Advanced and End‐Stage Renal Disease

Chronic kidney disease (CKD) affects 13% of the US population.[1][1] Although a significant proportion of these patients progress to end‐stage renal disease (ESRD) requiring renal replacement therapy (RRT)[2][2] or renal transplantation, cardiovascular disease remains the most common cause of

BILATERAL INTRARENAL ADRENAL GLANDS IN CADAVERIC DONOR KIDNEYS RESEMBLING RENAL CELL CARCINOMA ON INTRAOPERATIVE FROZEN SECTION

Ectopic adrenal tissue has been observed in a variety of sites. We report an unusual case of bilateral symmetrical intrarenal adrenal glands in cadaveric donor kidneys which were suspicious for renal cell carcinoma on intraoperative frozen section. CASE REPORT A 46-year-old man and a 64-year-old woman with end stage renal disease underwent cadaveric renal transplantation from the same donor. The donor was a 43-year-old woman with a history of myocardial infarction and congestive heart failure whose cause of death was subarachnoid hemorrhage. The first recipient received the left donor kidney. At transplantation the left donor adrenal gland was noted to be densely adherent to the upper pole of the donor kidney. No obvious masses were noted and adrenalectomy, thought to be complete, was performed before transplantation. The procedure was performed without incident and the patient was brought to the recovery room in stable condition. The second recipient received the right donor kidney. Before transplantation the right donor adrenal gland was also noted to be closely applied to the upper pole of the kidney but no nodularity or mass was noted. Most of the adrenal gland was excised and the donor kidney was successfully transplanted. Following reperfusion and completion of the ureteral anastomosis, there appeared to be a thickened area at the upper pole of the donor kidney. Frozen section biopsy of the suspicious lesion was interpreted as a small oncocytic tumor, probable oncocytoma. However, the possibility of a chromophobe renal cell carcinoma could not be excluded (fig. 1). With the suspicion of a possible malignant renal neoplasm, the donor kidney was removed before closure. After finding a possible neoplasm in the right donor kidney and a densely adherent adrenal gland on the left donor kidney, reexploration of the first transplant recipient was undertaken. Two 1.5 cm. pieces of tissue were excised from the site where the adrenal would normally be found. Frozen section of this specimen was identical to that of the contralateral side. Nephrectomy was performed. Final pathological analysis of both specimens proved to be intrarenal adrenal gland (fig. 2, A). A fat stain showed that the cells contained lipid, and immunostains of these cells for cytokeratin and epithelial membrane antigen were negative. In addition, an endothelial marker, CD34, showed columns of these cells to be separated by well-defined sinusoids. These sinusoids were in continuity and insinuated into the paratubular capillary network and tubules in the adjacent renal paren

C. Walton Lillehei, MD, PhD: a father of open-heart surgery

The challenge of performing heart surgery has both fascinated and intimidated surgeons. At the end of the 19th century, leaders in surgery and medicine pronounced that surgeons who tried to suture the heart would lose the respect of their colleagues and that no method or discovery could alter the problems associated with repair of the heart (Theodor Bilroth, 1883, and Stephen Paget, 1896). With the gauntlet laid down, the combined dictums fell to the successful repair of a cardiac injury in 1896 by Ludwig Rehn. However, the problems of elective operations within the heart remained a challenge for another half a century. The ultimate successes of a number of pioneers opened wide a new era in open-heart surgery, enabling corrections of both congenital and acquired heart defects. A giant among those giants was C. Walton Lillehei. Clarence Walton Lillehei was born in Edina, Minnesota, on October 23, 1918. His father was a dentist, and his mother was a professional pianist. C. Walton was the eldest of 3 sons. He had such dexterous skill that he reportedly built a motorcycle from spare parts and took apart and reassembled the engine of a Model T Ford without the assistance of an instruction manual. Despite skipping 2 years of elementary school, Lillehei was, at best, a mediocre student in high school. He nearly failed chemistry. Some of his instructors predicted poor college performance. Yet, after entering the University of Minnesota in the fall of 1935, he graduated in 1939 with distinction and went on to the University of Minnesota Medical School. There, Lillehei excelled academically, with the exception of 3 C’s, including 1, ironically, in his surgery clerkship. Throughout his college and medical school career, Lillehei adopted the motto “Work hard, play hard,” a philosophy to which he adhered throughout the rest of his life. Lillehei was a second-year medical student when he met Dr. Owen H. Wangensteen, the young chief of surgery with a passion for research and experimentation. Medical school education was accelerated during World War II, and by 1942, Lillehei graduated with both a medical degree and a master’s degree in physiology. After completing his internship, he began military service as a first lieutenant in the Army Medical Corps and was sent to Europe. By the time he returned in 1945, he was a lieutenant colonel and had received the Bronze Star for “Meritorious Services in Support of Combat Operations” in Anzio, Italy. After making but 1 application to surgical residency—the University of Minnesota, under Wangensteen—Lillehei began his formal surgical training in 1946. During the next few years, Lillehei met and worked with Dr. Richard Varco, the department’s closed-heart specialist (Figure 1). Lillehei recognized the difficulties, limitations, and excitement of operating on the closed, beating heart, but before he was able to pursue his interest, his life and career took an unexpected turn. In late 1949 Lillehei noted a small mass just anterior to his left ear that he presumed to be harmless and benign. He put off its excision until February 1950. Dr. David State removed it along with a portion of the parotid gland. Wangensteen and State were shocked with the final pathology report—lymphosarcoma. Incredulous, Wangensteen had the specimen evaluated at 4 other institutions, but all the “second opinions” concurred. Wangensteen finally disclosed this information to Lillehei after about 4 months’ delay. The prognosis for lymphosarcoma was dismal in those pre-chemotherapy days, and perhaps somewhat in desperation, Lillehei agreed to undergo further resection by Wangensteen. After a radical transmediastinal

Results of crossmatch between chimpanzee lymphocytes and sera of highly sensitized potential renal transplant recipients

Background: We tested the hypothesis that patients with a high frequency of lymphocytotoxic antibodies against human cells are not highly sensitized to major histocompatibility complexes expressed by chimpanzee cells. Methods: Sera from six “hopelessly” sensitized patients (percentage reactive antibodies (PRA)  > 99%) on the renal transplant waiting list were crossmatched with peripheral blood lymphocytes from 10 chimpanzees. Lymphocytotoxic antibodies reacting with chimpanzee peripheral blood lymphocytes were identified. Results: Three of the six patients with a high frequency of lymphocytotoxic antibodies against human cells had no xenospecific antibodies. Conclusion: Patients with a high frequency of lymphocytotoxic antibodies against human cells are not all panel‐reactive to chimpanzees. Unilateral donor nephrectomy in non‐human primates may offer an opportunity for safe expansion of the donor organ pool for these patients.