Larry Melton - Academia.edu (original) (raw)
Papers by Larry Melton
Dialysis & Transplantation, 2010
Proceedings (Baylor University. Medical Center), 2015
We report a late presentation of adenovirus-induced renal allograft and bladder infection causing... more We report a late presentation of adenovirus-induced renal allograft and bladder infection causing azotemia and hemorrhagic cystitis in a patient 5 years after simultaneous kidney-pancreas transplantation. Adenovirus has been increasingly recognized as a cause of morbidity and mortality in both solid organ and stem cell transplant recipients. We wish to emphasize the importance of early detection, as treatment options involve reduction of immunosuppression, followed by the addition of antiviral agents and supportive care.
Proceedings (Baylor University. Medical Center), 2010
The success of pancreas transplantation has improved over the past several decades with advanceme... more The success of pancreas transplantation has improved over the past several decades with advancements in surgical technique, immunosuppressive medicines, and immunologic testing. We retrospectively reviewed our experience with pancreas transplantation from 1995 to 2008. At the Baylor Regional Transplant Program, 151 pancreas transplants were performed in 147 patients: 135 were simultaneous pancreas-kidney transplants, 10 were pancreas transplants after kidney transplants, and 6 were pancreas transplants alone. Follow-up information was available for 138 patients. The 1-year acute cellular rejection rate was 31.6%; the 30-day surgical reexploration rate was 10%; and the technical failure rate was 5.3%. Five-year pancreas graft survival rates were 67% for simultaneous pancreas and kidney transplants and 50% for pancreas transplants after kidney transplants. These outcomes exceed expected results as calculated by the Scientific Registry of Transplant Recipients. In addition, the median ...
Clinical Immunology and Immunopathology, 1989
Transplantation, 2001
The calcineurin inhibitors cyclosporine and tacrolimus are both known to be nephrotoxic. Their us... more The calcineurin inhibitors cyclosporine and tacrolimus are both known to be nephrotoxic. Their use in orthotopic liver transplantation (OLTX) has dramatically improved success rates. Recently, however, we have had an increase of patients who are presenting after OLTX with end-stage renal disease (ESRD). This retrospective study examines the incidence and treatment of ESRD and chronic renal failure (CRF) in OLTX patients. Patients receiving an OLTX only from June 1985 through December of 1994 who survived 6 months postoperatively were studied (n=834). Our prospectively collected database was the source of information. Patients were divided into three groups: Controls, no CRF or ESRD, n=748; CRF, sustained serum creatinine >2.5 mg/dl, n=41; and ESRD, n=45. Groups were compared for preoperative laboratory variables, diagnosis, postoperative variables, survival, type of ESRD therapy, and survival from onset of ESRD. At 13 years after OLTX, the incidence of severe renal dysfunction was 18.1% (CRF 8.6% and ESRD 9.5%). Compared with control patients, CRF and ESRD patients had higher preoperative serum creatinine levels, a greater percentage of patients with hepatorenal syndrome, higher percentage requirement for dialysis in the first 3 months postoperatively, and a higher 1-year serum creatinine. Multivariate stepwise logistic regression analysis using preoperative and postoperative variables identified that an increase of serum creatinine compared with average at 1 year, 3 months, and 4 weeks postoperatively were independent risk factors for the development of CRF or ESRD with odds ratios of 2.6, 2.2, and 1.6, respectively. Overall survival from the time of OLTX was not significantly different among groups, but by year 13, the survival of the patients who had ESRD was only 28.2% compared with 54.6% in the control group. Patients developing ESRD had a 6-year survival after onset of ESRD of 27% for the patients receiving hemodialysis versus 71.4% for the patients developing ESRD who subsequently received kidney transplants. Patients who are more than 10 years post-OLTX have CRF and ESRD at a high rate. The development of ESRD decreases survival, particularly in those patients treated with dialysis only. Patients who develop ESRD have a higher preoperative and 1-year serum creatinine and are more likely to have hepatorenal syndrome. However, an increase of serum creatinine at various times postoperatively is more predictive of the development of CRF or ESRD. New strategies for long-term immunosuppression may be needed to decrease this complication.
Transplantation, 2004
Background. Acute renal failure developing after orthotopic liver transplantation (OLTx) requirin... more Background. Acute renal failure developing after orthotopic liver transplantation (OLTx) requiring renal replacement heralds a poor prognosis. Our center has previously reported a 1-year survival of only 41.8%. We undertook this study to determine whether we could identify preoperative and perioperative factors that would predict which patients are at risk. Methods. OLTxs performed between January 1, 1996, and December 31, 2001, were included in our retrospective database review. Combined kidney-liver transplants or patients with preoperative renal replacement therapy (RRT) were excluded. A total of 724 OLTxs were studied, which were divided into group I: no RRT, nϭ637; group II: hemodialysis only post-OLTx, nϭ17; and group III: continuous RRT post-OLTx, nϭ70. Univariate and stepwise logistic multivariate analyses were performed. Results. Preoperative serum creatinine greater than 1.9 mg/dL (odds ratio [OR] 3.57), preoperative blood urea nitrogen greater than 27 mg/dL (OR 2.68), intensive care unit stay more than 3 days (OR 10.23), and Model for End-Stage Liver Disease score greater than 21 (OR 2.5) were significant. A clinical prediction model was constructed: probability of requiring dialysis posttransplantϭ(Ϫ2.4586ϩ1.2726 [creatinine Ͼ1.9] ϩ 0.9858 [blood urea nitrogen Ͼ27] ϩ 0.4574 [Model for End-Stage Liver Disease score Ͼ21] ϩ 1.1625 [intensive care unit days Ͼ3]). A clinical prediction rule for patients with a score greater than 0.12 was applied to OLTx recipients who underwent transplantation in 2002. A total of 15 of 20 patients who received RRT and 111 of 121 who did not were correctly classified with the model. Conclusions. This model allowed us to identify patients at high risk for developing the need for RRT postoperatively. Strategies for these patients to prevent or ameliorate acute renal failure and reduce the need for RRT postoperatively are needed.
Transplantation, 2001
The need for renal replacement therapy (RRT) either before or after orthotopic liver transplant (... more The need for renal replacement therapy (RRT) either before or after orthotopic liver transplant (OLTX) has been reported to be a poor prognostic indicator for survival. Use of continuous veno-venous hemodialysis (CVVHD) for RRT has been reported in three series of OLTX patients with high 90-day mortality rates of 57-60%. We have examined our patient population to determine the effect of necessity and type of RRT on patient survival after OLTX. We analyzed 1535 OLTX that were performed at our institution from 1985 through 1999, 1037 from 1985 to 1995 (period I) and 498 from 1996 to 1999 (period II). Combined liver-kidney transplants were excluded from analysis. Hospital dialysis unit records and a prospectively maintained database on all OLTX patients served as the source of data. Patients were classified into groups defined on whether or not they received RRT, when they received RRT, and the type of RRT. Groups were compared for preoperative intensive care unit status, time on the waiting list, laboratory variables, 90-day postoperative mortality, 1-year patient survival, and absolute survival. Use of RRT increased from 8.29% in period I to 12.45% in period II, along with increased median waiting times. In period I, patients receiving preoperative RRT had a 90-day mortality (0%) and a 1-year survival (89.5%) almost identical to those patients who never required RRT (1.7% and 90.6%). Patients who developed acute renal failure postoperatively requiring RRT, however, had a 90-day mortality of 28.6% and a 1-year survival of 55%. In period II, patients requiring RRT had a 90-day mortality of 39.7% and a 1-year actuarial survival of 54.5% compared with 6.9% and 88.6% in patients never requiring RRT. Patients treated with CVVHD had a 90-day mortality of 42% compared with 25% in patients treated with hemodialysis alone. However, patients receiving CVVHD both pre- and postoperatively had a 90-day mortality of 27.7% vs. 50% in those patients who only received CVVHD postoperatively. Patients who developed acute renal failure postoperatively, which required RRT, regardless of therapy, had a 1-year survival of only 41.0% compared with a 1-year survival of 73.6% in those patients started on RRT preoperatively, P=0.03. The need for RRT has increased along with waiting time in OLTX patients. Patients developing the need for RRT postoperatively have an increased 90-day mortality and lower 1-year survival with the highest being present in patients receiving CVVHD, which was started postoperatively. These findings may reflect a trend toward a sicker population awaiting OLTX and emphasize the negative impact of renal failure on survival after OLTX.
Transplantation, 2005
Liver transplantation (LTX) corrects the enzymatic defect responsible for type 1 primary hyperoxa... more Liver transplantation (LTX) corrects the enzymatic defect responsible for type 1 primary hyperoxaluria (PH1). It has been advocated in combination with kidney transplantation (KTX) in patients with renal failure from PH1 because KTX alone can result in early graft loss. A 58-year-old male patient with PH1 on hemodialysis underwent resection of the left lateral segment of the liver followed by orthotopic auxiliary left lateral segment liver transplantation and kidney transplantation from a deceased donor. The serum oxalate dropped from 34.8 micromol/L before transplant to 3.6-8.3 in the first months posttransplant to <1 micromol/L (normal range 0.4-3.0). One year after posttransplant, the patient has an iothalamate glomerular filtration rate of 58 ml/min. Orthotopic auxiliary LTX is an alternative to whole LTX in PH1. By using a split deceased donor liver, it does not deprive the donor pool and protects the recipient from liver failure in case of graft loss.
Transplantation Journal, 2004
Transplantation, 2010
The immunosuppressive medications that have contributed greatly to the success of liver transplan... more The immunosuppressive medications that have contributed greatly to the success of liver transplantation are also associated with posttransplant renal dysfunction. We reviewed measured glomerular filtration rate (GFR) data from patients who underwent transplantation more than 10 years ago to assess whether results from specific time points can predict renal failure. The GFR data were obtained at initial evaluation (IE), at month 3, and at years 1, 2, 5, 10, and 15. Two groupings were compared, one based on GFR at IE and the other at month 3. Patients were further stratified into three GFR (mL/min/1.73 m2) groups: G1, GFR more than 80; G2, GFR 60 to 80; and G3, GFR less than 60. A total of 592 liver transplant recipients met the inclusion criteria; 114 had paired GFR data from IE to year 15. Analysis of paired and censored data based on IE GFR showed that 62.2% of G3 patients developed renal failure by year 5; another 6.7% did so by year 10 (P=0.027). The month 3 GFR data showed that 56.3% of G3 patients developed renal failure by year 5; another 15.6% did so by year 10. Surprisingly, 37.0% of G2 patients experienced renal failure by year 5; another 11.1% did so by year 10 (P=0.0024). The month 3 data indicate a slow but steady decline in GFR over years. The lower the initial GFR is after transplant, the sooner renal failure develops. Patients with GFR less than 60 mL/min per 1.73 m2 at month 3 have a higher risk of renal failure; however, those who avoid renal failure seem to maintain renal function long term.
Transplant Infectious Disease, 2010
Disseminated adenovirus (ADV) infection in solid organ transplant patients is associated with hig... more Disseminated adenovirus (ADV) infection in solid organ transplant patients is associated with high mortality. Limited studies have shown bene¢t from using cidofovir (CDV), as well as intravenous immunoglobulin (IVIG). In this study, we report 2 renal transplant patients who presented with fever and pulmonary in¢ltrates. Both patients continued to worsen despite antibiotic therapy. Bronchoalveolar lavage viral culture and serum polymerase chain reaction (PCR) were positive for ADV. Patients were treated with CDV, IVIG, and reduction in immunosuppression. A progressive decline in serum ADV DNA by PCR correlated with clinical improvement and pulmonary in¢ltrates improved. Both patients recovered. Allograft function was preserved although reversible acute kidney injury was observed in both patients. To the best of our knowledge, this is the ¢rst successful use of CDVand IVIG in renal transplant patients with disseminated ADV infection.
Liver Transplantation, 2009
The incidence of acute kidney injury (AKI) has been reported to vary between 17% and 95% post-ort... more The incidence of acute kidney injury (AKI) has been reported to vary between 17% and 95% post-orthotopic liver transplantation. This variability may be related to the absence of a uniform definition of AKI in this setting. The purpose of this study was to identify the degree of AKI that is associated with long-term adverse outcome. Furthermore, to determine the best definition (for use in future studies) of AKI not requiring dialysis in post-liver transplant patients, we retrospectively reviewed the effect of 3 definitions of AKI post-orthotopic liver transplantation on renal and patient outcome between 1997 and 2005. We compared patients with AKI to a control group without AKI by each definition. AKI was defined in 3 groups as an acute rise in serum creatinine, from the pretransplant baseline, of >0.5 mg/dL, >1.0 mg/dL, or >50% above baseline to a value above 2 mg/dL. In all groups, the glomerular filtration rate was significantly lower at both 1 and 2 years post-transplant. Patient survival was worse in all groups. Graft survival was worse in all groups. The incidence of AKI was highest in the group with a rise in creatinine of >0.5 mg/dL (78%) and lowest in patients with a rise in creatinine of >50% above 2.0 mg/dL (14%). Even mild AKI, defined as a rise in serum creatinine of >0.5 mg/dL, was associated with reduced patient and graft survival. However, in comparison with the other definitions, the definition of AKI with the greatest impact on patient's outcome post-liver transplant was a rise in serum creatinine of >50% above baseline to >2 mg/dL.
Human Immunology, 2010
Aim: Patient X, offered a 0-Ag mismatch kidney, had a historical serum with donor specific antibo... more Aim: Patient X, offered a 0-Ag mismatch kidney, had a historical serum with donor specific antibody (A66), based on single antigen beads (SAB). Per protocol, flow crossmatch (FCXM) was performed because X was "sensitized," but with current serum only (1 st transplant). FCXM was negative, but anti-A66 enigma still required explanation.
Dialysis & Transplantation, 2009
Clinical Transplantation, 2010
A significant number of patients awaiting liver transplantation have associated renal failure and... more A significant number of patients awaiting liver transplantation have associated renal failure and renal dysfunction is associated with increased morbidity and mortality after LT. There has been a recent increase in the number of CLKT in adults. The common indications for CLKT in children are different from those of adults and include metabolic diseases affecting the kidney with or without liver dysfunction and congenital developmental abnormalities affecting both organs. The results are generally encouraging among these groups of patients. Early evaluation and listing of patients before they become severely ill or have major systemic manifestations of their metabolic problem are important.
Cellular Immunology, 1991
It has been documented that interleukin-6 (IL-6) supports the proliferation of purified, anti-CD3... more It has been documented that interleukin-6 (IL-6) supports the proliferation of purified, anti-CD3stimulated murine T cells. We found that stimulation of human peripheral blood mononuclear cells (PBMCs) with anti-CD3 induced a significant accumulation of IL-6 mRNA, indicating that antigen-mediated T-cell activation may involve IL-6 release from accessory cells. Phytohemagglutinin (PHA) had little effect upon IL-6 gene expression. In keeping with these findings. anti-IL-6 reduced but did not abolish anti-CD3-mediated proliferation of PBMCs, but had no significant effect upon PHA-stimulated proliferation. The addition of recombinant (r) IL-6 enhanced the proliferation of anti-CD3-stimulated PBMCs and increased the accumulation of IL-2 mRNA in PHA-stimulated PBMCs during the first 5 hr of culture. Nuclear run-off experiments did not reveal significant changes in IL-2 transcription in PHA plus rIL-6-treated PBMCs attempting to assume that IL-6 mediates stabilization of IL-2 mRNA. However, monitoring of partially spliced IL-2 mRNA by polymerase chain reaction revealed a clear increase in IL-2 heteronuclear RNA. Thus IL-6 increases the rate of IL-2 transcription which was not detectable by conventional in vitro transcription assays. We conclude that anti-CD3 triggers T-cell proliferation through a process that is partially but not entirely dependent upon release of IL-6. IL-6. in turn, supports IL-2 transcription. Insofar as anti-CD3 mimicks antigen-triggered activation of the T-cell receptor complex, IL-6 appears to support the early immune response by augmenting antigen-triggered IL-2 gene eXpr&OII.
British Journal of Clinical Pharmacology, 2007
To compare the pharmacokinetics of mycophenolic acid (MPA) and its metabolite (MPAG) when mycophe... more To compare the pharmacokinetics of mycophenolic acid (MPA) and its metabolite (MPAG) when mycophenolate mofetil (MMF) is administered in combination with sirolimus or ciclosporin (CsA) in renal allograft recipients. Safety and efficacy (biopsyproven acute rejection (BPAR)) were also assessed.
Dialysis & Transplantation, 2010
Proceedings (Baylor University. Medical Center), 2015
We report a late presentation of adenovirus-induced renal allograft and bladder infection causing... more We report a late presentation of adenovirus-induced renal allograft and bladder infection causing azotemia and hemorrhagic cystitis in a patient 5 years after simultaneous kidney-pancreas transplantation. Adenovirus has been increasingly recognized as a cause of morbidity and mortality in both solid organ and stem cell transplant recipients. We wish to emphasize the importance of early detection, as treatment options involve reduction of immunosuppression, followed by the addition of antiviral agents and supportive care.
Proceedings (Baylor University. Medical Center), 2010
The success of pancreas transplantation has improved over the past several decades with advanceme... more The success of pancreas transplantation has improved over the past several decades with advancements in surgical technique, immunosuppressive medicines, and immunologic testing. We retrospectively reviewed our experience with pancreas transplantation from 1995 to 2008. At the Baylor Regional Transplant Program, 151 pancreas transplants were performed in 147 patients: 135 were simultaneous pancreas-kidney transplants, 10 were pancreas transplants after kidney transplants, and 6 were pancreas transplants alone. Follow-up information was available for 138 patients. The 1-year acute cellular rejection rate was 31.6%; the 30-day surgical reexploration rate was 10%; and the technical failure rate was 5.3%. Five-year pancreas graft survival rates were 67% for simultaneous pancreas and kidney transplants and 50% for pancreas transplants after kidney transplants. These outcomes exceed expected results as calculated by the Scientific Registry of Transplant Recipients. In addition, the median ...
Clinical Immunology and Immunopathology, 1989
Transplantation, 2001
The calcineurin inhibitors cyclosporine and tacrolimus are both known to be nephrotoxic. Their us... more The calcineurin inhibitors cyclosporine and tacrolimus are both known to be nephrotoxic. Their use in orthotopic liver transplantation (OLTX) has dramatically improved success rates. Recently, however, we have had an increase of patients who are presenting after OLTX with end-stage renal disease (ESRD). This retrospective study examines the incidence and treatment of ESRD and chronic renal failure (CRF) in OLTX patients. Patients receiving an OLTX only from June 1985 through December of 1994 who survived 6 months postoperatively were studied (n=834). Our prospectively collected database was the source of information. Patients were divided into three groups: Controls, no CRF or ESRD, n=748; CRF, sustained serum creatinine >2.5 mg/dl, n=41; and ESRD, n=45. Groups were compared for preoperative laboratory variables, diagnosis, postoperative variables, survival, type of ESRD therapy, and survival from onset of ESRD. At 13 years after OLTX, the incidence of severe renal dysfunction was 18.1% (CRF 8.6% and ESRD 9.5%). Compared with control patients, CRF and ESRD patients had higher preoperative serum creatinine levels, a greater percentage of patients with hepatorenal syndrome, higher percentage requirement for dialysis in the first 3 months postoperatively, and a higher 1-year serum creatinine. Multivariate stepwise logistic regression analysis using preoperative and postoperative variables identified that an increase of serum creatinine compared with average at 1 year, 3 months, and 4 weeks postoperatively were independent risk factors for the development of CRF or ESRD with odds ratios of 2.6, 2.2, and 1.6, respectively. Overall survival from the time of OLTX was not significantly different among groups, but by year 13, the survival of the patients who had ESRD was only 28.2% compared with 54.6% in the control group. Patients developing ESRD had a 6-year survival after onset of ESRD of 27% for the patients receiving hemodialysis versus 71.4% for the patients developing ESRD who subsequently received kidney transplants. Patients who are more than 10 years post-OLTX have CRF and ESRD at a high rate. The development of ESRD decreases survival, particularly in those patients treated with dialysis only. Patients who develop ESRD have a higher preoperative and 1-year serum creatinine and are more likely to have hepatorenal syndrome. However, an increase of serum creatinine at various times postoperatively is more predictive of the development of CRF or ESRD. New strategies for long-term immunosuppression may be needed to decrease this complication.
Transplantation, 2004
Background. Acute renal failure developing after orthotopic liver transplantation (OLTx) requirin... more Background. Acute renal failure developing after orthotopic liver transplantation (OLTx) requiring renal replacement heralds a poor prognosis. Our center has previously reported a 1-year survival of only 41.8%. We undertook this study to determine whether we could identify preoperative and perioperative factors that would predict which patients are at risk. Methods. OLTxs performed between January 1, 1996, and December 31, 2001, were included in our retrospective database review. Combined kidney-liver transplants or patients with preoperative renal replacement therapy (RRT) were excluded. A total of 724 OLTxs were studied, which were divided into group I: no RRT, nϭ637; group II: hemodialysis only post-OLTx, nϭ17; and group III: continuous RRT post-OLTx, nϭ70. Univariate and stepwise logistic multivariate analyses were performed. Results. Preoperative serum creatinine greater than 1.9 mg/dL (odds ratio [OR] 3.57), preoperative blood urea nitrogen greater than 27 mg/dL (OR 2.68), intensive care unit stay more than 3 days (OR 10.23), and Model for End-Stage Liver Disease score greater than 21 (OR 2.5) were significant. A clinical prediction model was constructed: probability of requiring dialysis posttransplantϭ(Ϫ2.4586ϩ1.2726 [creatinine Ͼ1.9] ϩ 0.9858 [blood urea nitrogen Ͼ27] ϩ 0.4574 [Model for End-Stage Liver Disease score Ͼ21] ϩ 1.1625 [intensive care unit days Ͼ3]). A clinical prediction rule for patients with a score greater than 0.12 was applied to OLTx recipients who underwent transplantation in 2002. A total of 15 of 20 patients who received RRT and 111 of 121 who did not were correctly classified with the model. Conclusions. This model allowed us to identify patients at high risk for developing the need for RRT postoperatively. Strategies for these patients to prevent or ameliorate acute renal failure and reduce the need for RRT postoperatively are needed.
Transplantation, 2001
The need for renal replacement therapy (RRT) either before or after orthotopic liver transplant (... more The need for renal replacement therapy (RRT) either before or after orthotopic liver transplant (OLTX) has been reported to be a poor prognostic indicator for survival. Use of continuous veno-venous hemodialysis (CVVHD) for RRT has been reported in three series of OLTX patients with high 90-day mortality rates of 57-60%. We have examined our patient population to determine the effect of necessity and type of RRT on patient survival after OLTX. We analyzed 1535 OLTX that were performed at our institution from 1985 through 1999, 1037 from 1985 to 1995 (period I) and 498 from 1996 to 1999 (period II). Combined liver-kidney transplants were excluded from analysis. Hospital dialysis unit records and a prospectively maintained database on all OLTX patients served as the source of data. Patients were classified into groups defined on whether or not they received RRT, when they received RRT, and the type of RRT. Groups were compared for preoperative intensive care unit status, time on the waiting list, laboratory variables, 90-day postoperative mortality, 1-year patient survival, and absolute survival. Use of RRT increased from 8.29% in period I to 12.45% in period II, along with increased median waiting times. In period I, patients receiving preoperative RRT had a 90-day mortality (0%) and a 1-year survival (89.5%) almost identical to those patients who never required RRT (1.7% and 90.6%). Patients who developed acute renal failure postoperatively requiring RRT, however, had a 90-day mortality of 28.6% and a 1-year survival of 55%. In period II, patients requiring RRT had a 90-day mortality of 39.7% and a 1-year actuarial survival of 54.5% compared with 6.9% and 88.6% in patients never requiring RRT. Patients treated with CVVHD had a 90-day mortality of 42% compared with 25% in patients treated with hemodialysis alone. However, patients receiving CVVHD both pre- and postoperatively had a 90-day mortality of 27.7% vs. 50% in those patients who only received CVVHD postoperatively. Patients who developed acute renal failure postoperatively, which required RRT, regardless of therapy, had a 1-year survival of only 41.0% compared with a 1-year survival of 73.6% in those patients started on RRT preoperatively, P=0.03. The need for RRT has increased along with waiting time in OLTX patients. Patients developing the need for RRT postoperatively have an increased 90-day mortality and lower 1-year survival with the highest being present in patients receiving CVVHD, which was started postoperatively. These findings may reflect a trend toward a sicker population awaiting OLTX and emphasize the negative impact of renal failure on survival after OLTX.
Transplantation, 2005
Liver transplantation (LTX) corrects the enzymatic defect responsible for type 1 primary hyperoxa... more Liver transplantation (LTX) corrects the enzymatic defect responsible for type 1 primary hyperoxaluria (PH1). It has been advocated in combination with kidney transplantation (KTX) in patients with renal failure from PH1 because KTX alone can result in early graft loss. A 58-year-old male patient with PH1 on hemodialysis underwent resection of the left lateral segment of the liver followed by orthotopic auxiliary left lateral segment liver transplantation and kidney transplantation from a deceased donor. The serum oxalate dropped from 34.8 micromol/L before transplant to 3.6-8.3 in the first months posttransplant to <1 micromol/L (normal range 0.4-3.0). One year after posttransplant, the patient has an iothalamate glomerular filtration rate of 58 ml/min. Orthotopic auxiliary LTX is an alternative to whole LTX in PH1. By using a split deceased donor liver, it does not deprive the donor pool and protects the recipient from liver failure in case of graft loss.
Transplantation Journal, 2004
Transplantation, 2010
The immunosuppressive medications that have contributed greatly to the success of liver transplan... more The immunosuppressive medications that have contributed greatly to the success of liver transplantation are also associated with posttransplant renal dysfunction. We reviewed measured glomerular filtration rate (GFR) data from patients who underwent transplantation more than 10 years ago to assess whether results from specific time points can predict renal failure. The GFR data were obtained at initial evaluation (IE), at month 3, and at years 1, 2, 5, 10, and 15. Two groupings were compared, one based on GFR at IE and the other at month 3. Patients were further stratified into three GFR (mL/min/1.73 m2) groups: G1, GFR more than 80; G2, GFR 60 to 80; and G3, GFR less than 60. A total of 592 liver transplant recipients met the inclusion criteria; 114 had paired GFR data from IE to year 15. Analysis of paired and censored data based on IE GFR showed that 62.2% of G3 patients developed renal failure by year 5; another 6.7% did so by year 10 (P=0.027). The month 3 GFR data showed that 56.3% of G3 patients developed renal failure by year 5; another 15.6% did so by year 10. Surprisingly, 37.0% of G2 patients experienced renal failure by year 5; another 11.1% did so by year 10 (P=0.0024). The month 3 data indicate a slow but steady decline in GFR over years. The lower the initial GFR is after transplant, the sooner renal failure develops. Patients with GFR less than 60 mL/min per 1.73 m2 at month 3 have a higher risk of renal failure; however, those who avoid renal failure seem to maintain renal function long term.
Transplant Infectious Disease, 2010
Disseminated adenovirus (ADV) infection in solid organ transplant patients is associated with hig... more Disseminated adenovirus (ADV) infection in solid organ transplant patients is associated with high mortality. Limited studies have shown bene¢t from using cidofovir (CDV), as well as intravenous immunoglobulin (IVIG). In this study, we report 2 renal transplant patients who presented with fever and pulmonary in¢ltrates. Both patients continued to worsen despite antibiotic therapy. Bronchoalveolar lavage viral culture and serum polymerase chain reaction (PCR) were positive for ADV. Patients were treated with CDV, IVIG, and reduction in immunosuppression. A progressive decline in serum ADV DNA by PCR correlated with clinical improvement and pulmonary in¢ltrates improved. Both patients recovered. Allograft function was preserved although reversible acute kidney injury was observed in both patients. To the best of our knowledge, this is the ¢rst successful use of CDVand IVIG in renal transplant patients with disseminated ADV infection.
Liver Transplantation, 2009
The incidence of acute kidney injury (AKI) has been reported to vary between 17% and 95% post-ort... more The incidence of acute kidney injury (AKI) has been reported to vary between 17% and 95% post-orthotopic liver transplantation. This variability may be related to the absence of a uniform definition of AKI in this setting. The purpose of this study was to identify the degree of AKI that is associated with long-term adverse outcome. Furthermore, to determine the best definition (for use in future studies) of AKI not requiring dialysis in post-liver transplant patients, we retrospectively reviewed the effect of 3 definitions of AKI post-orthotopic liver transplantation on renal and patient outcome between 1997 and 2005. We compared patients with AKI to a control group without AKI by each definition. AKI was defined in 3 groups as an acute rise in serum creatinine, from the pretransplant baseline, of >0.5 mg/dL, >1.0 mg/dL, or >50% above baseline to a value above 2 mg/dL. In all groups, the glomerular filtration rate was significantly lower at both 1 and 2 years post-transplant. Patient survival was worse in all groups. Graft survival was worse in all groups. The incidence of AKI was highest in the group with a rise in creatinine of >0.5 mg/dL (78%) and lowest in patients with a rise in creatinine of >50% above 2.0 mg/dL (14%). Even mild AKI, defined as a rise in serum creatinine of >0.5 mg/dL, was associated with reduced patient and graft survival. However, in comparison with the other definitions, the definition of AKI with the greatest impact on patient's outcome post-liver transplant was a rise in serum creatinine of >50% above baseline to >2 mg/dL.
Human Immunology, 2010
Aim: Patient X, offered a 0-Ag mismatch kidney, had a historical serum with donor specific antibo... more Aim: Patient X, offered a 0-Ag mismatch kidney, had a historical serum with donor specific antibody (A66), based on single antigen beads (SAB). Per protocol, flow crossmatch (FCXM) was performed because X was "sensitized," but with current serum only (1 st transplant). FCXM was negative, but anti-A66 enigma still required explanation.
Dialysis & Transplantation, 2009
Clinical Transplantation, 2010
A significant number of patients awaiting liver transplantation have associated renal failure and... more A significant number of patients awaiting liver transplantation have associated renal failure and renal dysfunction is associated with increased morbidity and mortality after LT. There has been a recent increase in the number of CLKT in adults. The common indications for CLKT in children are different from those of adults and include metabolic diseases affecting the kidney with or without liver dysfunction and congenital developmental abnormalities affecting both organs. The results are generally encouraging among these groups of patients. Early evaluation and listing of patients before they become severely ill or have major systemic manifestations of their metabolic problem are important.
Cellular Immunology, 1991
It has been documented that interleukin-6 (IL-6) supports the proliferation of purified, anti-CD3... more It has been documented that interleukin-6 (IL-6) supports the proliferation of purified, anti-CD3stimulated murine T cells. We found that stimulation of human peripheral blood mononuclear cells (PBMCs) with anti-CD3 induced a significant accumulation of IL-6 mRNA, indicating that antigen-mediated T-cell activation may involve IL-6 release from accessory cells. Phytohemagglutinin (PHA) had little effect upon IL-6 gene expression. In keeping with these findings. anti-IL-6 reduced but did not abolish anti-CD3-mediated proliferation of PBMCs, but had no significant effect upon PHA-stimulated proliferation. The addition of recombinant (r) IL-6 enhanced the proliferation of anti-CD3-stimulated PBMCs and increased the accumulation of IL-2 mRNA in PHA-stimulated PBMCs during the first 5 hr of culture. Nuclear run-off experiments did not reveal significant changes in IL-2 transcription in PHA plus rIL-6-treated PBMCs attempting to assume that IL-6 mediates stabilization of IL-2 mRNA. However, monitoring of partially spliced IL-2 mRNA by polymerase chain reaction revealed a clear increase in IL-2 heteronuclear RNA. Thus IL-6 increases the rate of IL-2 transcription which was not detectable by conventional in vitro transcription assays. We conclude that anti-CD3 triggers T-cell proliferation through a process that is partially but not entirely dependent upon release of IL-6. IL-6. in turn, supports IL-2 transcription. Insofar as anti-CD3 mimicks antigen-triggered activation of the T-cell receptor complex, IL-6 appears to support the early immune response by augmenting antigen-triggered IL-2 gene eXpr&OII.
British Journal of Clinical Pharmacology, 2007
To compare the pharmacokinetics of mycophenolic acid (MPA) and its metabolite (MPAG) when mycophe... more To compare the pharmacokinetics of mycophenolic acid (MPA) and its metabolite (MPAG) when mycophenolate mofetil (MMF) is administered in combination with sirolimus or ciclosporin (CsA) in renal allograft recipients. Safety and efficacy (biopsyproven acute rejection (BPAR)) were also assessed.