Excellent outcome using "impaired" standard criteria donors with elevated serum creatinine.

INTRODUCTION: To maximize organ utilization, the United Network for Organ Sharing (UNOS) encourages use of Expanded Criteria Donors (ECD). However, Standard Criteria Donors (SCD) may also be under-utilized, some centers discarding kidneys with serum creatinine (S.Cr) >2.0 at nephrectomy. Our experience with the use of such "impaired'' kidneys was reviewed retrospectively. RESULTS: From January 1, 2003 to October 1, 2006, of 130 DD kidneys transplanted at our center, 26 were ECD. Also, 22 kidneys were from Impaired SCD (ISCD), with mean S.Cr 3.2 (2.1-4.4) at nephrectomy; eight of these had S.Cr >4.0. For these 22 ISCD, mean age was 22 yrs (11-42), sex: 16 Males; race:12 Caucasians/10 African-Americans; All had evidence of rhabdomyolysis (Mean peak CPK 11,924 u/l). Thirty-seven percent came from outside OPOs. Recipient demographics: age 45 years; sex 50% male, 45% African-American. Mean HLA match was 1; dialysis was required in 28% within the first week. Mean length of stay was 10.7 days. Average discharge S.Cr was 4.2. All kidneys are currently functioning (S.Cr at 3 months, 6 months and 1 year 1.6, 1.7 and 1.7 respectively). CONCLUSION: An elevated creatinine should not be the only cause for discarding deceased donor kidneys.

Demographics and response to therapeutic plasma exchange in pediatric renal transplantation for focal glomerulosclerosis: a single center experience.

Recurrence of FSGS following renal transplantation in pediatric patients is reported as 20-57%. Records of 37 pediatric patients transplanted for FSGS between 1990 and 2005 at a single center were reviewed. Recurrence of disease was assessed by nephrotic range proteinuria and/or FSGS on biopsy. Response to TPE was defined as urine protein to creatinine ratio <0.2. Forty-nine percent of patients were African American, 38% were Caucasian. Fifty-four percent received kidneys from deceased donors and 46% from live donors. Seven patients received preemptive TPE prior to transplantation. Two of these seven patients recurred in the transplanted kidney (28%). Recurrent FSGS occurred in 16 of 37 patients (46%), all of whom received TPE. Recurrence occurred within one month in 12 of 37 patients (32%); eight remitted with TPE (67%). Four of 12 patients failed to respond to TPE. Four of 37 patients (14%) recurred more than one month after transplantation and underwent TPE; three-fourths of patients remitted (75%). Twenty-one of 37 patients (54%) did not recur. One and five yr graft survivals were 84% and 67%, respectively. Median graft survival was 6.7 yr (5.2-10.3). Despite recurrence, FSGS patients can achieve sustained graft function.

Acute renal failure in a pediatric kidney allograft recipient treated with intravenous immunoglobulin for parvovirus B19 induced pure red cell aplasia.

Infection with parvovirus B19 (PV-B19) after solid organ transplantation may cause pure red cell aplasia (PRCA). Intravenous immunoglobulin (IVIg) may be of benefit in clearing the infection. Acute renal failure is a known adverse effect of IVIg administration. A 14-yr-old male received a cadaveric renal transplant. Three weeks after surgery he developed symptomatic anemia (hemoglobin 4.5 g/dL, reticulocyte count 0.2%). Anti-PV-B19 IgM and IgG titers, which had been negative pretransplant, were positive. He received two IVIg infusions as treatment for the PV-B19 infection. Four days after the IVIg infusions he developed non-oliguric acute renal failure (ARF) with a rise in serum creatinine from 1 to 1.8 mg/dL. Allograft biopsy showed changes consistent with an osmotic load. Anemia and the renal failure resolved after transfusions and IVIg. PV-B19 infection in immunosuppressed transplant recipients is associated with significant morbidity and may respond to IVIg therapy. High sucrose IVIg preparations may be associated with renal failure in renal allograft recipients. Adding PV-B19 testing of the donor and recipient to the standard pretransplant evaluation may be beneficial in diagnosing and managing a potential infection. If IVIg is to be used it may be safer to use a sucrose-free IVIg preparation.

The effect of sirolimus on sex hormone levels of male renal transplant recipients.

BACKGROUND: It is unclear whether sirolimus, a newer immunosuppressive agent, widely used in renal transplantation, affects male sex hormone levels or sexual function. METHODS: Sex hormone profiles in male renal transplant recipients were obtained and compared between a sirolimus-treated group and a group not on sirolimus in a cross-sectional study. Both groups also completed a sexual dysfunction questionnaire. RESULTS: Sixty-six subjects were evaluated, 32 in the sirolimus group and 34 in the control group. Total testosterone level was significantly lower in the sirolimus group than the control group (393.3 +/- 188 vs. 537.4 +/-232 pg/mL; p = 0.08) while follicle stimulating hormone and luteinizing hormone levels were significantly higher in the sirolimus group (12.8 +/- 14 vs. 6.0 +/- 5, p = 0.013; 10.9 +/- 14 vs. 4.7 +/- 4, p = 0.018, respectively). There was a significant negative correlation between 24-h sirolimus trough and total testosterone levels (p < 0.03). By multiple regression analysis, use of sirolimus was independently associated with decreased total testosterone level. There was no significant difference in subjective sexual dysfunction as assessed by questionnaire scores between the two groups. There was no correlation between questionnaire scores and total testosterone level. CONCLUSION: Sirolimus is associated with decreased total testosterone levels in male renal transplant recipients. It is unclear whether sirolimus may affect other aspects of sexual function.

Successful rescue therapy with plasmapheresis and intravenous immunoglobulin for acute humoral renal transplant rejection.

Plasmapheresis (PP) and intravenous immunoglobulin (IVIg) remove donor-specific antibodies, a cause of acute humoral rejection (AHR). We describe the use of PP and IVIg as rescue therapy for AHR. The records of 143 renal transplants performed between October 1, 2000 and April 1, 2002 were reviewed. Patients who underwent PP and IVIg therapy for AHR were identified. The data reviewed included age, sex, source of transplant, number of human leukocyte antigen mismatches, transplant number, number of PP and IVIg treatments, dose of IVIg, time of AHR, serum creatinine (SCr) level at AHR, SCr level after PP and IVIg at 3 months, days to achieve 30% decline in SCr, and graft survival. Immunosuppression included basiliximab induction, tacrolimus, and prednisone (+/- sirolimus or mycophenolate mofetil [CellCept, Roche Pharmaceutical, Nutley, NJ]). PP was followed by IVIg infusion. Nine patients were treated for AHR with PP and IVIg. All nine patients demonstrated biopsy-proven AHR. One graft was lost. Mean 3-month and 1-year SCr levels were 1.9 and 1.8, respectively, in the remaining eight patients. AHR in renal transplantation can be effectively treated with PP and IVIg.

Inhibitory effect of brachytherapy on intimal hyperplasia in arteriovenous fistula.

PURPOSE: To determine whether endovascular radiation can inhibit intimal hyperplasia in a swine model of hemodialysis access. MATERIALS AND METHODS: Polytetrafluoroethylene arteriovenous grafts (6 mm in diameter) were placed between the common carotid artery and the external jugular vein bilaterally in 8 pigs. Two days after the surgery, fistulography was performed. Gamma radiation (12 Gy) was delivered endovascularly to one of the grafts at the venous anastomosis by using an iridium(192) source. Thus, the other graft in each pig served as an untreated control. Fistulas were evaluated with fistulography or venography 6 week after radiation. All grafts were then harvested for histological and immunohistochemical examination. RESULTS: Seven grafts on the treated side and 5 grafts on the control side remained patent for at least 6 weeks. Angiography demonstrated that the percentage stenosis at the venous anastomosis was significantly lower for the treated group (15.9 +/- 14.1 versus 32.6 +/- 16.7%, P = 0.045). Histopathologic analyses revealed that the mean intimal area and maximal intimal thickness were significantly lower with reduced smooth muscle cell proliferation at the venous anastomosis on the treated side compared to the control side (0.68 +/- 0.30 versus 1.06 +/- 0.29 mm(2), P = 0.017, and 0.18 +/- 0.08 versus 0.26 +/- 0.07 mm, P = 0.004, respectively). The residual lumen was significantly greater for the treated group (1.59 +/- 0.42 versus 1.06 +/- 0.37 mm(2), P = 0.031). No significant differences were found in the area, nor maximal thickness in the vein either proximal or distal to the anastomosis between the two groups. CONCLUSIONS: In an animal model of hemodialysis access, brachytherapy with iridium(192) delivered 2 days after graft implantation reduces intimal hyperplasia and stenosis at the venous anastomosis. The reduced smooth-muscle cells found in the radiated veins suggests that brachytherapy may exert its effect on neointimal formation by inhibition of smooth muscle cell proliferation.

Prevention of bone loss in renal transplant recipients: a prospective, randomized trial of intravenous pamidronate.

Renal transplant recipients are at risk of developing bone abnormalities that result in bone loss and bone fractures. These are related to underlying renal osteodystrophy, hypophosphatemia, and immunosuppressive treatment regimen. Although bisphosphonates are useful in ameliorating bone mineral loss after transplantation, it is not known whether their use in renal transplant patients leads to excessive suppression of bone turnover and increased incidence of adynamic bone disease. A randomized, prospective, controlled, clinical trial was conducted using the bisphosphonate pamidronate intravenously in patients with new renal transplants. Treatment subjects (PAM) received pamidronate with vitamin D and calcium at baseline and at months 1, 2, 3, and 6. Control (CON) subjects received vitamin D and calcium only. During months 6 to 12, the subjects were observed without pamidronate treatment. Biochemical parameters of bone turnover were obtained monthly and, bone mineral density (BMD) was obtained at baseline and months 6 and 12. Bone biopsies for mineralized bone histology were obtained at baseline and at 6 mo in a subgroup of subjects who underwent scheduled living donor transplantation. PAM preserved bone mass at 6 and 12 mo as measured by bone densitometry and histomorphometry. CON had decreased vertebral BMD at 6 and 12 mo (4.8 +/- 0.08 and 6.1 +/- 0.09%, respectively). Biochemical parameters of bone turnover were similar in both groups at 6 and 12 mo. Bone histology revealed low turnover bone disease in 50% of the patients at baseline. At 6 mo, all of PAM had adynamic bone disease, whereas 50% of CON continued to have or developed decreased bone turnover. Pamidronate preserved vertebral BMD during treatment and 6 mo after cessation of treatment. Pamidronate treatment was associated with development of adynamic bone histology. Whether an improved BMD with adynamic bone histology is useful in maintaining long-term bone health in renal transplant recipients requires further study.

Angiotensin-converting enzyme inhibition induces apoptosis in erythroid precursors and affects insulin-like growth factor-1 in posttransplantation erythrocytosis.

A number of studies suggest that erythropoietin (Ep), angiotensin II, and insulin-like growth factor (IGF-1) are involved in the pathogenesis of posttransplantation erythrocytosis (PTE). Angiotensin-converting enzyme inhibitors (ACEI) are the treatment of choice in PTE, but their mechanism of action is unclear. It was shown previously that ACEI added directly to cultures of erythroid precursors from patients with PTE inhibit colony growth. In this report, the effect of ACEI on CD34+ erythroid precursor apoptosis was studied, as were hematocrit (Hct), Ep, IGF-1, and IGF-binding protein 3 (IGF-BP3) levels. Ten patients with PTE, 10 transplant control patients, and 7 normal control subjects were studied. Peripheral blood CD34+ cells were isolated, and apoptosis was assessed by annexin assay and DNA laddering before and during ACEI therapy. At the same time, Hct, Ep, IGF-1, and IGF-BP3 levels were measured. Baseline CD34+ cell number, CD34+ apoptosis, Ep, IGF-1, and IGF-BP3 levels were the same between PTE and transplant control subjects. ACEI therapy was associated with a striking increase in CD34+ cell apoptosis and a decrease in Hct in both groups. In contrast to control subjects, patients with PTE on ACEI showed a significant decrease in IGF-1 levels and a greater percentage decrease in Hct. In normal control subjects, ACEI therapy was associated with a fall in Hct but no change in CD34+ cell apoptosis. In PTE, ACEI-related increase in erythroid progenitor apoptosis may partially explain the ACEI-associated decrease in Hct. However, it is not clear that erythroid precursor apoptosis is related to changes in IGF-1 or IGF-BP3.