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John D Scandling

Publications and source records attributed to John D Scandling.

11 recordsLinked to original sources
PubMed2006

The role of pre-emptive re-transplant in graft and recipient outcome.

BACKGROUND: The effect of the pre-emptive re-transplant, and of inter-transplant waiting time generally, on graft and recipient survival is not well established. METHODS: Analysis of the United States Renal Data System (USRDS) data (1/1/90 through 12/31/00; n = 92,844) was performed. Cox regression was used to analyse time to event, with an additional analysis to stratify by transplant era. RESULTS: Having a prior transplant, as well as the total number of transplants, was related to an increased risk of graft failure [hazard ratio (HR) 1.24, P<0.001 for history of prior transplant; HR 1.35 per transplant, P<0.001], but not to recipient death. The time waiting for re-transplant slightly worsened the risk for recipient mortality in the entire patient population and in the recipients of single re-transplant (HR 1.003 and 1.004 per month respectively, P<0.001), and for graft failure only in recipients of single re-transplant (HR 1.001 per month, P<0.05). Pre-emptive re-transplant (dialysis-free re-transplant or transplant within 6 days of last graft failure) increased the risk of graft failure (HR 1.36, P<0.001) and did not have any statistically significant effect on recipient survival. The longer duration of prior graft survival but not the type of the graft (living vs deceased) had protective effect on the consecutive graft and recipient survival. CONCLUSIONS: With the potential caveats associated with retrospective data analysis, these results suggest that pre-emptive re-transplantation is associated with increased risk of graft failure, while longer time on dialysis in between transplants is associated with negative effect upon graft and recipient survival in most patient subgroups. The optimal time in between graft failure and re-transplant was not evaluated in this study. Further prospective studies might be needed to confirm the observed effects.

Adolescent↗
PubMed2005

The role of pretransplantation renal replacement therapy modality in kidney allograft and recipient survival.

BACKGROUND: The effect of pretransplantation renal replacement therapy (RRT) modality on allograft and recipient survival outcome is not well understood. METHODS: We studied allograft and recipient survival by using US Renal Data System records from January 1, 1990, to December 31, 1999, with a follow-up period through December 31, 2000 (n = 92,844; 60% males; 70% white; 23% black). Pretransplantation and predominant RRT modality during the end-stage renal disease (ESRD) period and number and specific combinations of RRT modalities were evaluated. RESULTS: Compared with hemodialysis (HD), a Cox model showed that peritoneal dialysis (PD) immediately before transplantation predicts a 3% lower risk for graft failure (P < 0.05) and 6% lower risk for recipient death (P < 0.001). When predominant RRT modality was analyzed (modality used for > 50% of the ESRD time), PD (hazard ratio [HR], 0.97; P < 0.05) had a protective effect for graft survival compared with HD. Better recipient survival also was associated with PD (HR, 0.96; P < 0.05). Increased number of RRT modalities during the ESRD course was associated with increased risk for graft failure (HR, 1.04 per additional modality used; P < 0.005) and recipient death (HR, 1.11 per additional modality used; P < 0.001). Any combination or any single modality (except for PD + HD for graft survival and PD + HD and PD + HD + transplantation for recipient survival) had protective effects on graft and recipient survival compared with HD. CONCLUSION: Our results suggest that compared with PD, HD as an RRT modality immediately before transplantation or as a predominant RRT modality during the ESRD course, used alone or in combination with other RRT modalities, is associated with increased risks for graft failure and recipient death. Increased number of RRT modalities used during the ESRD course is associated with worsening of graft and recipient survival.

Adolescent↗
PubMed2004

Dual-kidney transplantation with organs from expanded criteria donors: a long-term follow-up.

BACKGROUND: Since 1995, dual-kidney transplantation using organs from marginal donors has been used at our center to expand the organ donor pool and decrease the waiting time for deceased donor kidney transplantation. This approach has allowed for a shorter waiting period without compromising outcome in the early posttransplant period. We now have 8-year follow-up in the first recipients. Older individuals were offered this option preferentially, because we reasoned that they would stand to benefit most from the shorter waiting period. METHODS: Patients aged 55 years or more who underwent either dual-kidney transplantation with expanded criteria donors or single-kidney transplantation with standard donors were included in this study. All expanded criteria donor organs were those that were refused by all other local transplant centers. The primary endpoints were recipient death and graft failure. RESULTS: Waiting time for dual-kidney transplantation was 440 +/- 38 days versus 664 +/- 51 days for single-kidney transplantation (P<0.01). The 8-year actuarial patient survivals for the single- and dual-kidney transplants were 74.1% and 82.1%, respectively. The 8-year actuarial graft survivals for the single- and dual-kidney transplants were 59.4% and 69.7%, respectively. CONCLUSIONS: Eight-year actuarial patient and graft survivals in older individuals who underwent dual-kidney transplantation are equivalent to those who underwent standard single-kidney transplantation. With the continuing organ shortage and increasing waiting times for cadaver kidney transplantation, dual-kidney transplantation using organs that would otherwise be discarded offers a good option for older individuals who may not withstand a long waiting period.

Actuarial Analysis↗
PubMed2004

Approaches to transplantation tolerance in humans.

Although transplantation tolerance to organ allografts has been achieved using a wide variety of immunologic interventions in laboratory animals, few tolerance induction protocols with complete immunosuppressive drug withdrawal have been tested in humans. Preclinical and clinical studies of the use of total lymphoid irradiation for the induction of chimeric and nonchimeric tolerance are summarized here.

Animals↗
PubMed2003

Prediction of 3-yr cadaveric graft survival based on pre-transplant variables in a large national dataset.

Pre- and post-transplant predictive factors of graft survival for optimal and expanded criteria grafts have been studied in the past. The goal of our study was to evaluate the recent large set of United Network of Organ Sharing records (1990-1998) to generate a prediction algorithm of 3-yr graft survival based on pre-transplant variables alone. The dataset of patients with end-stage renal disease and cadaveric kidney or kidney-pancreas transplantation (1990-1998) used in the study consisted of 37,407 records. Logistic regression (LM) and a tree-based model (TBM) were used to identify predictors of 3-yr allograft survival and to generate prediction algorithm. Donor and recipient demographic characteristics (age, race, and gender) and body mass index showed non-linear, while human leukocyte antigen match showed strong linear relationships with 3-yr graft survival. Prediction of the probability of graft survival from the model, achieved a good match with the observed survival of the separate dataset, with a correlation of r = 0.998 for LM and r = 0.984 for TBM. The positive predictive value (PV) of allograft survival with LM and TBM was 76.0% and the negative PV was 63 and 53.8% for LM and TBM, respectively. Both LM and the TBM can potentially be used in clinical practice for long-term prediction of kidney allograft survival based on pre-transplant variables.

Algorithms↗
PubMed2003

A randomized, placebo-controlled trial of IGF-1 for delayed graft function: a human model to study postischemic ARF.

BACKGROUND: Insulin-like growth factor (IGF-1) has been shown in animal models to accelerate recovery from acute renal failure (ARF). However, a therapeutic trial of recombinant human (rh) IGF-1 in patients with ARF in the intensive care unit (ICU) failed to demonstrate efficacy [1]. Such patients often had multiple organ failure, recurrent renal injury, and a delay of several days before commencing treatment. METHODS: To circumvent these confounding factors, we randomized recipients of cadaveric renal allografts to immediate (<5 hours) rhIGF-1 versus placebo therapy (100 mg/kg subcutaneously twice a day for 6 days). Preliminary observations 3 hours posttransplantation in an additional 44 patients revealed a creatinine clearance < or = 20 mL/min to predict protracted ARF. Thus, this value was used to determine study eligibility. RESULTS: Creatinine clearance prior to commencing treatment was not significantly different between the two groups (8 +/- 5 mL/min for IGF-1 and 7 +/- 6 mL/min for placebo; P = 0.39). Inulin clearance on day 7, the primary outcome measure, was 21 +/- 22 mL/min and 19 +/- 19 mL/min in the IGF-1 (N = 19) and placebo (N = 24) groups, respectively (P = 0.67). Secondary outcome measures, including nadir serum creatinines after 6 weeks and need for dialysis, also did not differ between the two groups. We performed an analysis of statistical power using the placebo arm of the trial. Defining a twofold increase above placebo in day 7 glomerular filtration rate (GFR) as of meaningful biologic significance, we determined that the modest sample size used in the present study is adequate. CONCLUSION: We, thus, conclude that (1) IGF-1 treatment is unlikely to benefit ARF and (2) the transplanted kidney is a good model to screen new agents for ARF that have demonstrated promise in animal trials.

Acute Kidney Injury↗
PubMed2002

Mixed chimerism and immunosuppressive drug withdrawal after HLA-mismatched kidney and hematopoietic progenitor transplantation.

BACKGROUND: Rodents and dogs conditioned with total-lymphoid irradiation (TLI), with or without antithymocyte globulin (ATG), have been shown to develop mixed chimerism and immune tolerance without graft-versus-host disease (GVHD) after the infusion of major histocompatability complex (MHC)-mismatched donor bone marrow cells given alone or in combination with an organ allograft. METHODS: Four human leukocyte antigen (HLA)-mismatched recipients of living donor kidney transplants were conditioned with TLI and ATG posttransplantation and infused with cyropreserved donor granulocyte colony-stimulating factor (G-CSF) "mobilized" hematopoietic progenitor (CD34+) cells (3-5x10(6) cells/kg) thereafter. Maintenance prednisone and cyclosporine dosages were tapered, and recipients were monitored for chimerism, GVHD, graft function, T-cell subsets in the blood, and antidonor reactivity in the mixed leukocyte reaction (MLR). RESULTS: Three of the four patients achieved multilineage macrochimerism, with up to 16% of donor-type cells among blood mononuclear cells without evidence of GVHD. Prolonged depletion of CD4+ T cells was observed in all four patients. Rejection episodes were not observed in the three macrochimeric recipients, and immunosuppressive drugs were withdrawn in the first patient by 12 months. Prednisone was withdrawn from a second patient at 9 months, and cyclosporine was tapered thereafter. CONCLUSIONS: Multilineage macrochimerism can be achieved without GVHD in HLA-mismatched recipients of combined kidney and hematopoietic progenitor transplants. Conditioning of the host with posttransplant TLI and ATG was nonmyeloablative and was not associated with severe infections. Recipients continue to be studied for the development of immune tolerance.

Adult↗
PubMed2002

Late post-transplant anemia in adult renal transplant recipients. An under-recognized problem?

Post-transplant anemia (PTA), a frequent complication during the first 3-6 months after transplant, is thought to be uncommon during the late post-transplant period. A study population of adults (> 18 years) transplanted during 1995 at Stanford University (n = 88) and University of North Carolina (n = 40) was selected. Data-collection points were 0, 1, 2, 3, 4 and 5 years post transplant. Anemia was defined as a hematocrit < 33 volume percentage. Thirty percent of patients were anemic at some time during the post-transplant period. The prevalence of PTA increased over time; by 5 years post transplant, 26% of the patients were anemic. Anemia occurred in 62.5% of patients converted from azathioprine to mycophenolate mofetil. A multivariate logistic regression model demonstrated a correlation between anemia and serum total CO2 (p = 0.002), BUN (p = 0.04), and creatinine (p = 0.045) at 1 year post transplant. At 5 years post transplant, only serum total CO2 (p = 0.0004) correlated with anemia. Thus, diminished renal excretory function and metabolic acidosis appear to be the most important correlates of late PTA. These findings should be interpreted in view of the fact that the newer immunosuppressive agents may have an even more profound effect on anemia and its recovery after transplantation.

Adult↗
PubMedDate not supplied

Validation of a screening protocol for identifying low-risk candidates with type 1 diabetes mellitus for kidney with or without pancreas transplantation.

BACKGROUND: Certain clinical risk factors are associated with significant coronary artery disease in kidney transplant candidates with diabetes mellitus. We sought to validate the use of a clinical algorithm in predicting post-transplantation mortality in patients with type 1 diabetes. We also examined the prevalence of significant coronary lesions in high-risk transplant candidates. METHODS: All patients with type 1 diabetes evaluated between 1991 and 2001 for kidney with/without pancreas transplantation were classified as high-risk based on the presence of any of the following risk factors: age >or=45 yr, smoking history >or=5 pack years, diabetes duration >or=25 yr or any ST-T segment abnormalities on electrocardiogram. Remaining patients were considered low risk. All high-risk candidates were advised to undergo coronary angiography. The primary outcome of interest was all-cause mortality post-transplantation. RESULTS: Eighty-four high-risk and 42 low-risk patients were identified. Significant coronary artery stenosis was detected in 31 high-risk candidates. Mean arterial pressure was a significant predictor of coronary stenosis (odds ratio 1.68; 95% confidence interval 1.14-2.46), adjusted for age, sex and duration of diabetes. In 75 candidates who underwent transplantation with median follow-up of 47 months, the use of clinical risk factors predicted all eight deaths. No deaths occurred in low-risk patients. A significant mortality difference was noted between the two risk groups (p = 0.03). CONCLUSIONS: This clinical algorithm can identify patients with type 1 diabetes at risk for mortality after kidney with/without pancreas transplant. Patients without clinical risk factors can safely undergo transplantation without further cardiac evaluation.

Age of Onset↗
PubMedDate not supplied

Kidney transplant candidate evaluation.

The practicing nephrologist is an indispensable component in the evaluation of the candidate for kidney transplantation, from referral to the transplant center to eventual transplantation, which now may be years later. Early referral may lead to preemptive transplantation, the ideal that has been achieved in 25% of living donor transplant cases. Annually approximately 30% of U.S. deceased donor kidneys are now transplanted under the allocation policies for zero human leukocyte antigen (HLA) mismatch kidneys and expanded criteria donor kidneys. Under either of these programs, candidates may receive a kidney offer soon after entering the wait-list, so prompt and complete evaluation and preparation by the practicing nephrologist is necessary for successful early transplantation. The remaining candidates require periodic review while ascending the wait-list and thorough repeat evaluation when nearing the top, as years may have passed since initial evaluation. Wait-list management is a major challenge faced by transplant centers, aggravated by the inexorable growth of the list. Active communication between the practicing nephrologist and the transplant center is essential to maintain the candidate's preparation for transplantation.

Comorbidity↗