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Biomedical subjects

L G Hunsicker

Publications and source records attributed to L G Hunsicker.

At least 19 recordsLinked to original sources
PubMed1999

The Banff 97 working classification of renal allograft pathology.

BACKGROUND: Standardization of renal allograft biopsy interpretation is necessary to guide therapy and to establish an objective end point for clinical trials. This manuscript describes a classification, Banff 97, developed by investigators using the Banff Schema and the Collaborative Clinical Trials in Transplantation (CCTT) modification for diagnosis of renal allograft pathology. METHODS: Banff 97 grew from an international consensus discussion begun at Banff and continued via the Internet. This schema developed from (a) analysis of data using the Banff classification, (b) publication of and experience with the CCTT modification, (c) international conferences, and (d) data from recent studies on impact of vasculitis on transplant outcome. RESULTS: Semiquantitative lesion scoring continues to focus on tubulitis and arteritis but includes a minimum threshold for interstitial inflammation. Banff 97 defines "types" of acute/active rejection. Type I is tubulointerstitial rejection without arteritis. Type II is vascular rejection with intimal arteritis, and type III is severe rejection with transmural arterial changes. Biopsies with only mild inflammation are graded as "borderline/suspicious for rejection." Chronic/sclerosing allograft changes are graded based on severity of tubular atrophy and interstitial fibrosis. Antibody-mediated rejection, hyperacute or accelerated acute in presentation, is also categorized, as are other significant allograft findings. CONCLUSIONS: The Banff 97 working classification refines earlier schemas and represents input from two classifications most widely used in clinical rejection trials and in clinical practice worldwide. Major changes include the following: rejection with vasculitis is separated from tubulointerstitial rejection; severe rejection requires transmural changes in arteries; "borderline" rejection can only be interpreted in a clinical context; antibody-mediated rejection is further defined, and lesion scoring focuses on most severely involved structures. Criteria for specimen adequacy have also been modified. Banff 97 represents a significant refinement of allograft assessment, developed via international consensus discussions.

Acute Disease↗
PubMed1998

Center-specific graft and patient survival rates: 1997 United Network for Organ Sharing (UNOS) report.

CONTEXT: Multiple comprehensive, risk-adjusted studies evaluating short-term surgical mortality have been reported previously. This report analyzes short-term and long-term outcomes, both nationally and at each individual transplant program, for all solid organ transplantations performed in the United States. OBJECTIVES: To report graft and patient survival rates for all solid organ transplantations, both nationally and at each specific transplant program in the United States, and to compare the expected survival rate with the actual survival rate of each individual program. DESIGN AND SETTING: Multivariate regression analysis of donor and recipient factors affecting graft and patient survival of all kidney, liver, pancreas, heart, lung, and heart-lung transplants reported to the United Network for Organ Sharing from 742 separate transplant programs. PATIENTS: A cohort of 97587 solid organ transplantations performed on 92966 recipients in the United States from January 1988 through April 1994. MAIN OUTCOME MEASURES: Short-term and conditional 3-year national and individual transplant program graft and patient survival rates overall and from 2 separate eras (era 1, January 1988-April 1992; era 2, May 1992-April 1994); comparison of actual center-specific performance with risk-adjusted expected performance and identification of centers with better-than-expected or worse-than-expected survival rates. RESULTS: One-year graft follow-up exceeded 98% and conditional 3-year follow-up exceeded 91% for all organs. Graft and patient survival improved significantly in era 2 compared with era 1 for all cadaver organs except heart, which remained the same. One-year cadaveric graft survival ranged from 81.5% for heart to 61.9% for heart-lung and 3-year conditional graft survival ranged from 91.3% for pancreas to 74.7% for lung. The percentage of programs whose actual 1-year graft survival was not different from or was better than their risk-adjusted expected survival ranged from 98.3% for heart-lung to 75.7% for liver. Most kidney, liver, and heart programs whose actual survival was significantly less than expected performed small numbers (less than the national average) of transplantations per year. CONCLUSIONS: Graft and patient survival for solid organ transplantations showed improvement over time. Conditional 3-year graft and patient survival rates were approximately 90% for all organs except for lung and heart-lung. The conditional 3-year survival rates were better than 1-year survival rates, indicating the major risk after transplantation occurs in the first year. The majority of transplant programs achieved actual survival rates not significantly different from their expected survival rates. Center effects were most significant within the first year after transplantation and had much less influence on long-term survival outcomes.

Actuarial Analysis↗
PubMed1997

Predictors of the progression of renal disease in the Modification of Diet in Renal Disease Study.

The Modification of Diet in Renal Disease (MDRD) Study examined the effects of dietary protein restriction and strict blood pressure control on the decline in glomerular filtration rate (GFR) in 840 patients with diverse renal diseases. We describe a systematic analysis to determine baseline factors that predict the decline in GFR, or which alter the efficacy of the diet or blood pressure interventions. Univariate analysis identified 18 of 41 investigated baseline factors as significant (P < 0.05) predictors of GFR decline. In multivariate analysis, six factors--greater urine protein excretion, diagnosis of polycystic kidney disease (PKD), lower serum transferrin, higher mean arterial pressure, black race, and lower serum HDL cholesterol--independently predicted a faster decline in GFR. Together with the study interventions, these six factors accounted for 34.5% and 33.9% of the variance between patients in GFR slopes in Studies A and B, respectively, with proteinuria and PKD playing the predominant role. The mean rate of GFR decline was not significantly related to baseline GFR, suggesting an approximately linear mean GFR decline as renal disease progresses. The 41 baseline predictors were also assessed for their interactions with the diet and blood pressure interventions. A greater benefit of the low blood pressure intervention was found in patients with higher baseline urine protein. None of the 41 baseline factors were shown to predict a greater or lesser effect of dietary protein restriction.

Blood Pressure↗
PubMed1996

Effect of grapefruit juice on cyclosporine pharmacokinetics in renal transplant patients.

This study investigated the effect of grapefruit juice on cyclosporine A (CsA) bioavailability in 10 renal transplant patients. Under CsA steady state conditions, patients were randomly administered their usual dose of CsA with either 8 ounces of grapefruit juice or 8 ounces of water. Using a crossover design, a 12-hr pharmacokinetic study was then conducted. Grapefruit juice increased the area under the concentration versus time curve (4218+/-1497 ng x hr/ml [grapefruit juice] vs. 3415+/-1288 ng x hr/ml [water], P=0.029) and 12-hr trough (244+/-214 ng x ml [grapefruit juice] vs. 132+/-56 ng x ml [water], P=0.09), but it did not change peak concentration (734+/-290 ng x ml [grapefruit juice] vs. 708+/-305 ng x ml [water], P=0.76). In addition, grapefruit juice delayed the time to peak concentration compared with water (5.4+/-3.0 hr [grapefruit juice] vs. 2.8+/-0.8 hr [water], P=0.025). These data suggest that concurrent administration of grapefruit juice with CsA will delay the absorption of CsA and increase the drug exposure of CsA without changing peak concentration.

Adult↗
PubMed1996

Effects of dietary protein restriction on the progression of advanced renal disease in the Modification of Diet in Renal Disease Study.

Patients with advanced renal disease randomized to the very low-protein diet group in the Modification of Diet in Renal Disease (MDRD) Study had a marginally (P = 0.066) slower mean glomerular filtration rate (GFR) decline compared with patients randomized to the low-protein diet group. The objective of these secondary analyses was to determine the relationship between achieved, in addition to prescribed, dietary protein intake and the progression of advanced renal disease. A randomized controlled trial was conducted in patients with chronic renal diseases of diverse etiology. The average follow-up was 2.2 years. Fifteen university hospital outpatient nephrology practices participated in the study, which comprised 255 patients aged 18 to 70 years with a baseline GFR 13 to 24 mL/min/1.73 m2 who participated in MDRD Study B. Patients with diabetes requiring insulin were excluded. The patients were given a low-protein (0.58 g/kg/d) or very low-protein (0.28 g/kg/d) diet supplemented with keto acids-amino acids (0.28 g/kg/d). Outcomes were measured by comparisons of protein intake from food or from food and supplement between randomized groups, and correlations of protein intake with rate of decline in GFR and time to renal failure or death. Comparison of the randomized groups showed that total protein intake from food and supplement was lower (P < 0.001) among patients randomized to the very low-protein diet (0.66 g/kg/d) compared with protein intake from food only in patients randomized to the low-protein diet (0.73 g/kg/d). In correlational analyses, we combined patients assigned to both diets and controlled for baseline factors associated with a faster progression of renal disease. A 0.2 g/kg/d lower achieved total protein intake (including food and supplement) was associated with a 1.15 mL/min/yr slower mean decline in GFR (P = 0.011), equivalent to 29% of the mean GFR decline. After adjusting for achieved total protein intake, no independent effect of prescription of the keto acid-amino acid supplement to slow the GFR decline could be detected. If the GFR decline is extrapolated until renal failure, a patient with a 29% reduction in the rate of GFR decline would experience a 41% prolongation in the time to renal failure. Additional analyses confirmed a longer time to renal failure in patients with lower total protein intake. In conclusion, these secondary analyses of the MDRD Study suggest that a lower protein intake, but not the keto acid-amino acid supplement, retards the progression of advanced renal disease. In patients with GFR less than 25 mL/min/1.73 m2, we suggest a prescribed dietary protein intake of 0.6 g/kg/d.

Adolescent↗
PubMed1995

Blood pressure control, proteinuria, and the progression of renal disease. The Modification of Diet in Renal Disease Study.

OBJECTIVE: To examine the relations among proteinuria, prescribed and achieved blood pressure, and decline in glomerular filtration rate in the Modification of Diet in Renal Disease Study. DESIGN: 2 randomized trials in patients with chronic renal diseases of diverse cause. SETTING: 15 outpatient nephrology practices at university hospitals. PATIENTS: 840 patients, of whom 585 were in study A (glomerular filtration rate, 25 to 55 mliters/min.1.73 m2) and 255 were in study B (glomerular filtration rate, 13 to 24 mliters/min.1.73 m2). Diabetic patients who required insulin were excluded. INTERVENTIONS: Patients were randomly assigned to a usual blood pressure goal (target mean arterial pressure, < or = 107 mm Hg for patients < or = 60 years of age and < or = 113 mm Hg for patients > or = 61 years of age) or a low blood pressure goal (target mean arterial pressure, < or = 92 mm Hg for patients < or = 60 years of age and < or = 98 mm Hg for patients > or = 61 years of age). MAIN OUTCOME MEASURES: Rate of decline in glomerular filtration rate and change in proteinuria during follow-up. RESULTS: The low blood pressure goal had a greater beneficial effect in persons with higher baseline proteinuria in both study A (P = 0.02) and study B (P = 0.01). Glomerular filtration rate declined faster in patients with higher achieved blood pressure during follow-up in both study A (r = -0.20; P < 0.001) and study B (r = -0.34; P < 0.001), and these correlations were stronger in persons with higher baseline proteinuria (P < 0.001 in study A; P < 0.01 in study B). In study A, the association between decline in glomerular filtration rate and achieved follow-up blood pressure was nonlinear (P = 0.011) and was stronger at higher mean arterial pressure. In both studies, the low blood pressure goal significantly reduced proteinuria during the first 4 months after randomization. This, in turn, correlated with a slower subsequent decline in glomerular filtration rate. CONCLUSIONS: Our study supports the concept that proteinuria is an independent risk factor for the progression of renal disease. For patients with proteinuria of more than 1 g/d, we suggest a target blood pressure of less than 92 mm Hg (125/75 mm Hg). For patients with proteinuria of 0.25 to 1.0 g/d, a target mean arterial pressure of less than 98 mm Hg (about 130/80 mm Hg) may be advisable. The extent to which lowering blood pressure reduces proteinuria may be a measure of the effectiveness of this therapy in slowing the progression of renal disease.

Adolescent↗
PubMed1995

Protein calculation from food diaries of adult humans underestimates values determined using a biological marker.

We evaluated the ability of a biological marker (nitrogen excretion expressed as protein) to accurately reflect the protein intake of 12 healthy subjects consuming a low protein diet (0.6 g protein/kg standard body wt). In this crossover study, protein intake was confirmed by chemically analyzing a duplicate of the constant diet each subject consumed for 3 d and by calculating protein content of self-selected diets recorded during two additional 3-d periods. Diet analysis matched excretion (difference 0.03 +/- 0.04 g protein/kg standard body wt, means +/- SEM). Self-selected intake manually calculated by subjects using educational materials matched the prescription [0.60 (0.42, 0.86) g protein/kg standard body wt, median (range)], but underestimated excretion by 0.18 +/- 0.02 g protein/kg standard body wt (means +/- SEM). Self-selected intake recalculated by the authors using a computerized database was only +0.05 (-0.08, +0.44) g protein/kg standard body wt higher than subjects' calculations, suggesting that discrepancies between databases and/or subject calculation errors only partially accounted for how greatly self-selected intake underestimated excretion. In a secondary analysis of self-selected intake, the three dietitian subjects consumed more energy and excreted less protein than nondietitians (137 +/- 4.9 vs. 94 +/- 3.5 kJ/standard body wt; 0.72 +/- 0.02 vs. 0.83 +/- 0.02 g protein/kg standard body wt), suggesting that adequate energy intake and/or additional training might improve agreement between intake and excretion. Thus, discrepancies between protein excretion and reported intake may reflect factors other than willful noncompliance.

Adult↗
PubMed1995

Chronic rejection in renal allografts: importance of cardiovascular risk factors.

Using a case-control method, we reviewed retrospectively renal transplants performed at University of Iowa Hospitals & Clinics between April, 1973 and May 29, 1991 to see if cardiovascular risk factors such as obesity, blood pressure, cholesterol, and tobacco use were important risk factors for development of chronic vascular rejection. Of 1161 transplants done during that time, 834 patients had renal allografts which functioned for greater than 365 days. From this subgroup we selected all surviving patients (n = 97) who had a functioning graft for greater than 365 days but whose graft subsequently failed. We also selected all patients (n = 26) who died with a functioning graft. Finally, we selected 52 control patients who were still living with functioning grafts, approximately matched to the study patients for date of transplant. We found no significant difference among the three groups in weight and weight changes, mean blood pressures, mean serum cholesterol values, or tobacco use. Our findings agree with previously published studies indicating a lack of correlation of cardiovascular risk factors with the development of chronic rejection of renal allografts in humans.

Adult↗
PubMed1995

Temporal changes of MR findings in central pontine myelinolysis.

We report central pontine myelinolysis in orthotopic liver transplant patients. Sequential MR imaging of these patients with central pontine myelinolysis shows progressive decrease of T2-weighted MR signal in the pons, which may not resolve despite complete neurologic recovery.

Adult↗
PubMed1995

Design of trials of methods to reduce late renal allograft loss: the price of success.

The excellent present outcomes of renal transplantation pose major challenges for the construction of future studies of interventions to reduce late renal allograft loss. Using current data on expected renal allograft outcomes, we performed power calculations to estimate the required size of trials of primary and secondary interventions in chronic renal allograft rejection. A primary prevention trial would require recruitment of 1500 patients over three years and is probably not feasible. A secondary intervention trial would require entry of only 126 patients and is still feasible. The difficulty of performing trials using graft failure as the primary study outcome has encouraged interest in use of surrogate endpoints such as acute rejection. Using the UNOS renal transplant data base, we examined changes over time in the frequency of acute rejection within the first year and the risk of subsequent graft loss. Changes in acute rejection rates were neither parallel to nor predictive of changes in the rate of late graft loss, providing no support for the use of acute rejection as a surrogate for late graft loss. Future continued improvement in renal transplant outcomes may require changes in traditional scientific and administrative methods for evaluating the impacts of proposed interventions.

Clinical Trials as Topic↗
PubMed1995

Long-term results of kidney transplantation: a single center experience.

Overall, patient and renal allograft survivals after cadaveric transplantation have improved significantly since the incorporation of CsA into the standard immunosuppressive regimen. Overall, patient and renal allograft survivals were significantly better for non-diabetic recipients when compared to diabetic recipients after cadaveric transplantation. Living-donor renal transplant recipients have a better outcome than cadaveric transplant recipients. Cardiovascular disease is the leading cause of death after renal transplantation. Death on dialysis accounted for the second largest number of posttransplant mortalities. Sepsis and malignancy remained the next most important causes of death after renal transplantation.

Academic Medical Centers↗
PubMed1994

The impact of HLA mismatches on the survival of first cadaveric kidney transplants.

BACKGROUND: The benefits of HLA-A, B, and DR matching of cadaveric kidney grafts and recipients remain controversial when viewed from the perspective of social equity and graft survival. METHODS: We estimated graft survival using proportional-hazards techniques, adjusting for patient and donor characteristics, for a series of 30,564 Medicare patients receiving a first cadaveric kidney transplant between 1984 and 1990. The effects of minimal achievable HLA mismatches and maximal matching on graft survival were estimated by simulated allocation of a sample of organs to a sample of 20,000 candidates for transplantation. RESULTS: The adjusted one-year graft survival was 84.3 percent for grafts with no mismatches and 77.0 percent for grafts with four mismatches. National rationing of donor organs to achieve minimal mismatching and maximal matching could potentially decrease the average number of HLA mismatches from 3.6 to 1.2, with a corresponding increase in the number of matches. As a consequence, projected five-year graft survival could potentially increase from 58.5 percent to 62.9 percent. This would be associated with a decrease in the proportion of kidneys allocated to black recipients from 22.2 to 15.0 percent. CONCLUSIONS: Under ideal circumstances, a policy of maximal matching of cadaveric renal transplants would increase five-year graft survival by a comparatively small 4.4 percentage points, but the actual benefit is likely to be smaller.

Adolescent↗
PubMed1994

The effect of transplant center volume on cardiac transplant outcome. A report of the United Network for Organ Sharing Scientific Registry.

OBJECTIVE: The number of cardiac transplant programs continues to increase despite no increase in the number of hearts available for transplantation. As a result, the majority of heart transplant centers perform extremely small numbers of transplant operations annually. To determine the effect of small transplantation volume on transplant outcome, the following study was performed. DESIGN: Using the Scientific Registry of the United Network for Organ Sharing, all cardiac transplant procedures from October 1987 through December 1991 were analyzed to determine whether center volumes affected cardiac transplant outcome. Patient survival rates for each center were determined, and the survival rates were modeled for the following patient variables: first transplantation or retransplantation, patient condition at the time of transplantation, patient underlying cardiac disease (congenital vs all others), and time. SETTING: All cardiac transplant centers in the United States were included in the analysis. PATIENTS: All patients undergoing cardiac transplantation in the United States from October 1987 through December 1991 were included in the analysis. MAIN OUTCOME MEASURE: The primary end point in this analysis was mortality. RESULTS: Throughout the entire study, of the 150 cardiac transplant centers, 35.3% of the centers were performing fewer than five cardiac transplantations per year, 53.3% were performing fewer than nine transplantations per year, and 61.3% were performing fewer than 12 transplantations per year, the minimum required for Medicare payment eligibility. Using the modeled survival rates, the risk of mortality decreased to a basal level in those centers performing between eight and 10 transplant operations per year. In centers performing fewer than nine transplantations, mortality increased sharply and exponentially. Dividing centers into those that performed nine or more transplantations per year (70 centers) and fewer than nine transplantations per year (80 centers), the increased risk of mortality at 1 month and 12 months was 40.3% and 33.1%, respectively, in centers performing fewer than nine cardiac transplantations per year (P < .001). Once the threshold of nine transplant procedures was met, those centers that were eligible for Medicare payment did not have significantly better survival than those centers not eligible for Medicare coverage. CONCLUSIONS: These data demonstrate that the risk of mortality at early and intermediate time points is substantially higher in low-volume cardiac transplant centers, which make up more than half of the centers performing cardiac transplantation in the United States.

Adolescent↗
PubMed1994

Treatment of severe cardiac allograft rejection with extracorporeal photochemotherapy.

Two patients were treated with photopheresis for marked cardiac allograft rejection with hemodynamic compromise that had become unresponsive to standard therapy. Multiple episodes of rejection had occurred, and initial response to standard therapy was favorable. However, progressive deterioration was documented by serial endomyocardial biopsies, fever, congestive heart failure, and abnormal cardiac catheterization findings. In the absence of retransplantation, death seemed imminent. Photopheresis was begun. Both patients received oral 8-methoxypsoralen and > or = 5 x 10(9) mononuclear cells were collected, treated with ultraviolet light A for 1.5 hours, and were reinfused. One procedure was performed weekly x4 and then monthly x5. Responses were striking with rapid loss of fever, improvement in exercise tolerance, normalization of cardiac hemodynamics, and improvement in endomyocardial biopsies. Although our experience with these two patients is anecdotal, photopheresis merits further study as treatment for severe cardiac allograft rejection.

Adult↗
PubMed1994

Simultaneous pancreas-kidney versus kidney-alone transplants in diabetics: increased risk of early cardiac death and acute rejection following pancreas transplants.

The decision between a simultaneous pancreas-kidney (SPK) or kidney-alone (KA) transplant for the treatment of diabetic end-stage renal disease depends on the risk-versus-benefit of each procedure. In this study we compared the mortality, morbidity, graft function and acute rejection after 88 SPK and 65 KA transplants. All acute rejection episodes were biopsy-proven. Patient survival was higher in the KA group (KA 92%, SPK 83%) at 1 year, but similar in both groups at 5 years (SPK 78%, KA 71%). Whereas myocardial infarction accounted for a similar proportion of deaths in both groups, sepsis and surgical complications were more common causes of death in the SPK group. The majority of cardiovascular deaths occurred early in the SPK group compared to the KA group. Kidney graft survival was similar at 1 year (SPK 79%, KA 81%) and 5 years (SPK 66%, KA 59%). Pancreas graft survival at 1 and 5 years was 75% and 60% respectively. Biopsy-proven acute rejection occurred more frequently in the SPK group (SPK 63%, KA 46%). Morbidity was greater in the SPK group and included vascular (SPK 19%, KA 3%), non-infectious urologic (SPK 23%, KA 3%) and infectious complications (SPK 86%, KA 33%). The majority of complications in the SPK group were related to the pancreas allograft. In summary, SPK transplants were associated with an increased risk of early cardiovascular death, greater morbidity and more frequent biopsy-proven acute rejection episodes. However, kidney graft survival was not affected by the addition of the pancreas allograft.

Adult↗
PubMed1993

The effect of angiotensin-converting-enzyme inhibition on diabetic nephropathy. The Collaborative Study Group.

BACKGROUND: Renal function declines progressively in patients who have diabetic nephropathy, and the decline may be slowed by antihypertensive drugs. The purpose of this study was to determine whether captopril has kidney-protecting properties independent of its effect on blood pressure in diabetic nephropathy. METHODS: We performed a randomized, controlled trial comparing captopril with placebo in patients with insulin-dependent diabetes mellitus in whom urinary protein excretion was > or = 500 mg per day and the serum creatinine concentration was < or = 2.5 mg per deciliter (221 mumol per liter). Blood-pressure goals were defined to achieve control during a median follow-up of three years. The primary end point was a doubling of the base-line serum creatinine concentration. RESULTS: Two hundred seven patients received captopril, and 202 placebo. Serum creatinine concentrations doubled in 25 patients in the captopril group, as compared with 43 patients in the placebo group (P = 0.007). The associated reductions in risk of a doubling of the serum creatinine concentration were 48 percent in the captopril group as a whole, 76 percent in the subgroup with a baseline serum creatinine concentration of 2.0 mg per deciliter (177 mumol per liter), 55 percent in the subgroup with a concentration of 1.5 mg per deciliter (133 mumol per liter), and 17 percent in the subgroup with a concentration of 1.0 mg per deciliter (88.4 mumol per liter). The mean (+/- SD) rate of decline in creatinine clearance was 11 +/- 21 percent per year in the captopril group and 17 +/- 20 percent per year in the placebo group (P = 0.03). Among the patients whose base-line serum creatinine concentration was > or = 1.5 mg per deciliter, creatinine clearance declined at a rate of 23 +/- 25 percent per year in the captopril group and at a rate of 37 +/- 25 percent per year in the placebo group (P = 0.01). Captopril treatment was associated with a 50 percent reduction in the risk of the combined end points of death, dialysis, and transplantation that was independent of the small disparity in blood pressure between the groups. CONCLUSIONS: Captopril protects against deterioration in renal function in insulin-dependent diabetic nephropathy and is significantly more effective than blood-pressure control alone.

Adult↗