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Sandy Feng

Publications and source records attributed to Sandy Feng.

At least 19 recordsLinked to original sources
PubMed2006

Optimizing living donor kidney graft function by donor-recipient pair selection.

BACKGROUND: With the rising prevalence of living donor kidney transplantations (LDKT), we increasingly encounter transplant candidates who present with multiple potential living donors. For a given candidate, it can be unclear which donor offers the best opportunity for optimal posttransplant graft function. This study was undertaken to determine the relative contributions of individual donor demographic factors on graft function following LDKT. METHODS: All LDKT donor-recipient pairs between January 1, 1999 and December 31, 2002 entered into the Scientific Registry of Transplant Recipients (SRTR) were reviewed. Suboptimal one year graft function was defined as a serum creatinine (Cr) greater than 1.5 mg/dL. RESULTS: Of 20,528 adult LDKTs performed, 8,603 donor-recipient pairs had complete donor, recipient, and one year graft function data. Over one third (36%) of all LDKTs had suboptimal one year graft function. Logistic regression identified simple recipient and donor characteristics associated with suboptimal one year graft function. Four recipient factors (age, gender, race, and size), three donor factors (age, gender, and size) and recipient-donor relatedness were used to derive an equation that predicts the risk of suboptimal one year graft function posed by each potential living donor for a given transplant candidate. CONCLUSIONS: In the setting of multiple potential living kidney donors, this quantitative tool may facilitate the choice of the optimal donor.

Adult↗
PubMed2006

Liver-specific loss of beta-catenin blocks glutamine synthesis pathway activity and cytochrome p450 expression in mice.

There is accumulating evidence that Wnt/beta-catenin signaling is involved in the regulation of liver development and physiology. The presence of genetic alterations resulting in constitutive beta-catenin stabilization in human and murine liver tumors also implicates this pathway in hepatocyte proliferation. In the present study, we generated hepatocyte-specific beta-catenin knockout mice to explore the role of beta-catenin in liver function. Conditional knockout mice were born at the expected Mendelian ratio and developed normally to adulthood, indicating beta-catenin is dispensable for essential liver function under normal breeding conditions. However, the liver mass of knockout mice was 20% less than those of mice in the control groups. Expression analysis revealed loss of genes required for glutamine synthesis in knockout mice. Loss of the liver glutamine synthesis pathway did not affect the blood ammonia level in mice fed a standard diet, yet, knockout mice showed significantly elevated blood ammonia levels with high-protein dietary feeding. Furthermore, the expression of two cytochrome P450 enzymes, CYP1A2 and CYP2E1, was almost completely abolished in livers from hepatocyte-specific beta-catenin knockout mice. Consequently, these mice were resistant to acetaminophen challenge, confirming the requirement of these cytochrome P450 enzymes for metabolism of xenobiotic substances. In conclusion, in addition to regulating hepatocyte proliferation, beta-catenin may also control multiple aspects of normal liver function.

Acetaminophen↗
PubMed2006

Trends over a decade of pediatric liver transplantation in the United States.

During the last 10 to 15 years, medical and surgical innovations have established pediatric liver transplantation as the optimal therapy for children suffering acute and chronic liver disease. We hypothesized that the profile of current pediatric liver transplant recipients would differ significantly from that of an earlier era. We collected and compared data regarding the characteristics of children undergoing liver transplantation alone in 2 eras separated by more than a decade from the Organ Procurement and Transplantation Network/United Network for Organ Sharing database. Transplant recipients from March 1, 2002 to December 31, 2004, compared to those from January 1, 1990, to December 31, 1992, tended to be more evenly distributed across age, race/ethnicity, and disease etiology. There was a major shift toward utilization of partial grafts from both deceased and living donors to achieve transplantation for the youngest children (<1 and 1-5 yr) in particular. However, in spite of these innovative transplant strategies and only a modest increase in demand for pediatric liver transplantation, wait list times for both pediatric candidates and recipients have still increased between eras. In conclusion, the sobering reality that mortality on the waiting list remains highest for the youngest pediatric liver candidates frames our challenge for the next decade.

Adolescent↗
PubMed2005

A prospective study on downstaging of hepatocellular carcinoma prior to liver transplantation.

In patients with hepatocellular carcinoma (HCC) exceeding conventional (T2) criteria for orthotopic liver transplantation (OLT), the feasibility and outcome following loco-regional therapy intended for tumor downstaging to meet T2 criteria for OLT are unknown. In this first prospective study on downstaging of HCC prior to OLT, the eligibility criteria for enrollment into a downstaging protocol included 1 lesion >5 cm and < or =8 cm, 2 or 3 lesions at least 1 >3 cm but < or =5 cm with total tumor diameter of < or =8 cm, or 4 or 5 nodules all < or =3 cm with total tumor diameter < or =8 cm. Patients were eligible for living-donor liver transplantation (LDLT) if tumors were downstaged to within proposed University of California, San Francisco (UCSF) criteria.13 A minimum follow-up period of 3 months after downstaging was required before cadaveric OLT or LDLT, with imaging studies meeting criteria for successful downstaging. Among the 30 patients enrolled, 21 (70%) met criteria for successful downstaging, including 16 (53%) who had subsequently received OLT (2 with LDLT), and 9 patients (30%) were classified as treatment failures. In the explant of 16 patients who underwent OLT, 7 had complete tumor necrosis, 7 met T2 criteria, but 2 exceeded T2 criteria. No HCC recurrence was observed after a median follow-up of 16 months after OLT. The Kaplan-Meier intention-to-treat survival was 89.3 and 81.8% at 1 and 2 yr, respectively. In conclusion, successful tumor downstaging can be achieved in the majority of carefully selected patients, but longer follow-up is needed to further access the risk of HCC recurrence after OLT.

Aged↗
PubMed2005

End stage polycystic kidney disease: indications and timing of native nephrectomy relative to kidney transplantation.

PURPOSE: We evaluated the indications for and outcome of pre-transplant, concomitant and post-transplant native nephrectomy in patients with end stage polycystic kidney disease (PCKD). MATERIALS AND METHODS: The records of 32 patients were retrospectively reviewed using the electronic database at our institution. RESULTS: Between January 1992 and December 2002, 171 patients with end stage PCKD received a kidney transplant at University of California-San Francisco. A total of 32 patients (18.7%) underwent pre-transplant (7, group 1), concomitant (16, group 2) or post-transplant (9, group 3) native nephrectomy. Of these patients 25 underwent bilateral nephrectomy. Median followup was 18 months. Indications for nephrectomy were hematuria, a renal mass and chronic pain in group 1, lack of space in group 2 and urinary tract infection in group 3. Mean operative time +/- SEM was 231 +/- 14, 370 +/- 24 and 208 +/- 14 minutes in groups 1 to 3, respectively (p = 0.001). Mean intraoperative blood loss was 533 +/- 105, 573 +/- 155 and 522 +/- 181 ml in groups 1 to 3, respectively (p not significant). Two group 2 patients required blood transfusions. Postoperative complications requiring surgical intervention included wound dehiscence in group 1 and abdominal bleeding in group 3. Mean hospital stay was comparable among groups 1 to 3 at 7 +/- 0.7, 8.6 +/- 1.2 and 6.3 +/- 0.6 days, respectively (p not significant). At 3 months mean serum creatinine was not significantly different between groups 2 and 3 at 1.3 +/- 0.1 and 1.5 +/- 0.2 mg/dl, respectively. CONCLUSIONS: Unilateral or bilateral nephrectomy for PCKD at transplantation is safe in terms of postoperative patient morbidity and graft function. We perform concomitant native nephrectomy when indicated, preferably in recipients of living donor kidney transplants.

Adult↗
PubMed2005

BKV in simultaneous pancreas-kidney transplant recipients: a leading cause of renal graft loss in first 2 years post-transplant.

With the introduction of more potent immunosuppressive agents, rejection has decreased in simultaneous pancreas/kidney transplant (SPK) recipients. However, as a consequence, opportunistic infections have increased. The purpose of this report is to outline the course of SPK patients who developed polyomavirus-associated nephropathy (PVAN). A retrospective review of 146 consecutive SPK recipients from January 1, 1996 to December 31, 2002 was performed. Immunosuppression, rejection and development of PVAN were reviewed. Nine patients were identified. All received induction with either OKT3 or thymoglobulin. Immunosuppression included tacrolimus/cyclosporine, MMF/azathioprine and sirolimus/prednisone. Two patients were treated for kidney rejection prior to the diagnosis of PVAN. Time to diagnosis was an average of 359.3 days post-transplantation. Immunosuppression was decreased but five ultimately lost function. However, none developed pancreatic abnormalities as demonstrated by normal glucose and amylase. Two underwent renal retransplantation after PVAN diagnosis and both have normal kidney function. PVAN was the leading cause of renal loss in SPK patients in the first 2 years after transplantation and is a serious concern for SPK recipients. The pancreas, however, is spared from evidence of infection, and no pancreatic rejection occurred when immunosuppression was decreased.

Adult↗
PubMed2005

Laparoscopic procurement of kidneys with multiple renal arteries is associated with increased ureteral complications in the recipient.

This study investigates the effect of renal artery multiplicity on donor and recipient outcomes after laparoscopic donor nephrectomy. Three-hundred and sixty-one sequential procedures were performed over a 4-year period. Forty-nine involved accessory renal arteries; of these, 36 required revascularization and 13 were small polar vessels and ligated. The 312 remaining kidneys with single arteries served as controls. Study variables included operative times, blood loss, hospital stay, graft function and donor and recipient complications. Kidneys with multiple revascularized arteries had a longer mean warm ischemia time (35.3 vs. 29.2 min, p = 0.0003), and more ureteral complications (6/36 vs. 10/312, p = 0.0013) than single-artery controls. In contrast, ligation of a small superior accessory artery had no significant effect on donor operative time, blood loss, or complication rate while providing similar recipient graft function compared to single-artery controls. Renal artery number is important in selecting the appropriate kidney for laparoscopic procurement. Given the current excellent results with right-sided donor nephrectomy, kidneys with single arteries should be preferentially procured, irrespective of side.

Adult↗
PubMed2005

Expanded criteria donor kidney allocation: marked decrease in cold ischemia and delayed graft function at a single center.

Expanded criteria donor (ECD) kidney allocation aims to increase utilization and facilitate placement. We implemented an ECD program for pre-consented candidates and studied whether ECD allocation decreased cold ischemia time and delayed graft function (DGF). We compared donor, recipient and transplant data for ECD transplants performed during the first year of our program to those performed in the preceding 5 1/2 years. Logistic regression identified risk factors for DGF. Of 356 candidates, 107 (30%) consented, 32 (9%) completed evaluation and 20 (6%) underwent ECD transplantation during the program's first year. The recent and historical ECD cohorts had similar donor and recipient characteristics, except that recent ECD recipients were older. The rate of donor kidney biopsy dropped from 85% to 24% (p < 0.001). Cold ischemia time decreased from 16.4 to 7.4 h (p < 0.001), as did the incidence of DGF from 43% to 15% (p = 0.031). Three independent risk factors for DGF emerged: recipient height (OR 1.21/10 cm; p = 0.008), >4 HLA mismatches (OR 20.46; p = 0.0033) and cold ischemia time (OR 1.24/h; p = 0.0036). We conclude the ECD designation provides a description of kidney quality that may obviate biopsy. ECD allocation decreased cold ischemia time and DGF, which may improve graft survival.

Aged↗
PubMed2004

Increased rejection in living unrelated versus living related kidney transplants does not affect short-term function and survival.

BACKGROUND: At our institution, increased kidney donation from unrelated donors accounts for a steady rise in live donor kidney transplantation rates. We compared outcomes of living related (LRT) versus living unrelated kidney transplants (LURT) and analyzed the effect of early rejection upon graft survival. METHODS: A retrospective analysis on 428 adult living donor kidney transplants was performed. Graft function and survival were compared between LRT and LURT and risk factors for 1-year rejection were defined by multivariate analysis. RESULTS: Between 1/1/97 and 12/31/01, 308 LRT and 120 LURT were performed at the University of California San Francisco. Donor age and number of mismatches were significantly higher in the LURT group. Patient and graft survival were similar in both groups. After a median follow-up of 26 months, graft survival was 94.8% (LRT) versus 93.3% (LURT). Five-year serum creatinine levels were comparable in both populations. One-year rejection was higher in the LURT group (30% vs. 18.5%; P<0.01). Rejection was influenced by the number of human leukocyte antigen mismatches. Other independent risk factors for early rejection were poor initial graft function, donor age greater than 55 years, and recipient body mass index greater than 30. Patients with poor initial graft function and early rejection had a statistically greater incidence of subtherapeutic tacrolimus trough levels on postoperative day 7. CONCLUSIONS: Despite a higher incidence of early rejection, LURT show similar function and survival compared with LRT. In high-risk patients receiving living unrelated renal transplants, consideration should be given to intensify initial immunosuppression to prevent early rejection episodes.

Adult↗
PubMed2004

Developmental context determines latency of MYC-induced tumorigenesis.

One of the enigmas in tumor biology is that different types of cancers are prevalent in different age groups. One possible explanation is that the ability of a specific oncogene to cause tumorigenesis in a particular cell type depends on epigenetic parameters such as the developmental context. To address this hypothesis, we have used the tetracycline regulatory system to generate transgenic mice in which the expression of a c-MYC human transgene can be conditionally regulated in murine hepatocytes. MYC's ability to induce tumorigenesis was dependent upon developmental context. In embryonic and neonatal mice, MYC overexpression in the liver induced marked cell proliferation and immediate onset of neoplasia. In contrast, in adult mice MYC overexpression induced cell growth and DNA replication without mitotic cell division, and mice succumbed to neoplasia only after a prolonged latency. In adult hepatocytes, MYC activation failed to induce cell division, which was at least in part mediated through the activation of p53. Surprisingly, apoptosis is not a barrier to MYC inducing tumorigenesis. The ability of oncogenes to induce tumorigenesis may be generally restrained by developmentally specific mechanisms. Adult somatic cells have evolved mechanisms to prevent individual oncogenes from initiating cellular growth, DNA replication, and mitotic cellular division alone, thereby preventing any single genetic event from inducing tumorigenesis.

Alleles↗
PubMed2004

Comparison of outcomes after delayed graft function: sirolimus-based versus other calcineurin-inhibitor sparing induction immunosuppression regimens.

BACKGROUND: Sirolimus (SRL) may increase the incidence of or prolong delayed graft function (DGF) after cadaveric renal transplantation. This study compares transplant outcomes of SRL-based induction immunosuppression (IS) with other calcineurin-inhibitor (CNI) sparing regimens in the DGF setting. METHODS: Adult cadaveric renal-transplant recipients who received transplants between January 1, 1997 and June 30, 2001 and experienced DGF (n=132) were divided into three groups by induction IS: A, depleting antibody (n=41); B, SRL (n=49); and C, neither (n=42). All recipients also received steroids and mycophenolate mofetil with delayed initiation of CNIs when good renal function returned. Patient survival, graft survival, and time to rejection within 1 year of transplantation were assessed by Kaplan-Meier analysis. One-year graft function was compared using Kruskal-Wallis and Fisher's exact tests. RESULTS: The SRL group had longer DGF duration (P=0.01). The three groups had comparable patient (P=0.27) and graft survival (P=0.69), but the depleting antibody group experienced less rejection (P=0.004). There were no clinically significant differences in 1-year graft function. CONCLUSIONS: In our analysis of a large and modern cohort of adult cadaveric transplant recipients with DGF, induction immunosuppression with a depleting antibody preparation reduced rejection, whereas SRL prolonged DGF duration. All three CNI-sparing induction IS regimens resulted in comparable patient survival, graft survival, and graft function.

Adult↗