Posttransplant hypertension.
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Cyclosporine↗
Biomedical subjects
J J Curtis
Publications and source records attributed to J J Curtis.
Living unrelated renal transplantation: progress and potential.
Transplant centers are turning to emotionally related or living unrelated kidney donors more often than in the past. Such donors are a benefit to the patient with end-stage renal disease, yet concern about their use persists. In the United States, the use of related donors has been well established in most centers. Nonetheless, there had been a reluctance to use nonrelatives that only recently has started to change. Most physicians agree that kidney transplant results are improved with living unrelated donor utilization. The transplant community needs to be watchful of the living unrelated donor operation. Both the welfare of the donor and the possibility of a "slippery slope" toward kidney bartering are considerations that need careful monitoring.
Evaluation Studies as Topic↗
Losartan, an angiotensin II type 1 receptor antagonist, lowers hematocrit in posttransplant erythrocytosis.
The mechanism by which angiotensin-converting enzyme inhibitors reduce red cell mass in renal transplant recipients with erythrocytosis is unclear. To examine the role of angiotensin II in this disorder, losartan (a competitive antagonist of the angiotensin II type 1 [AT1] receptor) was administered to 23 patients with erythrocytosis. Fourteen patients took 25 mg/d for 8 wk; nine others were treated with 50 mg/d for 8 wk. Hematocrit decreased from 0.527 +/- 0.027 to 0.487 +/- 0.045 after 8 wk (P < 0.01)--by at least 0.04 in 19 patients. Decrement in hematocrit in the initial 8 wk of therapy was significantly greater in patients administered 50 mg/d than in patients on 25 mg/d. Twelve of 14 patients initially treated with 25 mg/d showed a small change in hematocrit; the dose was increased to 50 mg/d for 8 more wk. Hematocrit decreased from 0.528 +/- 0.030 before losartan treatment to 0.483 +/- 0.055 after 16 wk (P < 0.01). After therapy, serum erythropoietin significantly decreased in eight patients with elevated baseline levels, but not in 15 patients with normal baseline levels; however, hematocrit significantly decreased in both groups. Losartan was withdrawn in 16 patients; hematocrit increased from 0.440 +/- 0.057 to 0.495 +/- 0.049 after 8.9 +/- 7.5 wk (P < 0.001), without change in serum erythropoietin. Thus, specific blockade of AT1 receptors inhibited erythropoiesis, suggesting a pathogenic role for angiotensin II in posttransplant erythrocytosis.
Angiotensin Receptor Antagonists↗
Neoral conversion from Sandimmune in maintenance renal transplant patients: an individualized approach.
When converting maintenance renal allograft recipients from Sandimmune (cyclosporin A [CsA]) to Neoral (CsA-microemulsion [CsA-ME]), a dose conversion ratio of 1:1 may not be optimal, in part because of the variability in absorption of the CsA formulation of cyclosporine. After conversion using a 1:1 dose ratio, an individualized approach to the management of dosing was applied. In this article, close monitoring, which began at the time of conversion, and rapid response to potentially meaningful changes in cyclosporine trough levels early in the postconversion course were used to maintain patients' cyclosporine troughs at preconversion levels. The results of cyclosporine dose changes after converting stable, maintenance renal transplant patients from CsA (once daily and twice daily) to CsA-ME (twice daily) during 52 wk of follow-up are reported. Most patients (87.2%) required CsA-ME dose reduction to maintain preconversion trough levels, and 64% of the patients attained their CsA-ME maintenance dose by study week 4. Logistic regression analysis identified one significant predictor concerning the week 52 CsA-ME dose: patients converted from CsA doses > or = 4.0 mg/kg per d were more likely to require dose reduction (P < 0.0001). Although firm guidelines for dose modification after conversion from CsA to CsA-ME cannot be provided because of the individual nature of cyclosporine absorption, an individualized approach to patient management is recommended. Patients with higher CsA doses before conversion are particularly likely to require dose reduction early in the postconversion course. With CsA-ME, good absorbers of cyclosporine remain good absorbers, or become better absorbers, whereas poor absorbers become good absorbers.
Adult↗
End-stage renal disease patients: referral for transplantation.
Patients who receive kidney transplants have a higher quality of life, a less costly form of therapy, and less risk of death than those who are treated with dialysis. This success of transplantation and a simultaneous lack of success in increasing the number of cadaveric organ donors has created a supply-demand crisis. The United Network of Organ Sharing has attempted to develop a fair allocation system for placing patients on waiting lists for kidney transplantation. An increase in the number of organs available would allow physicians to transplant patients earlier in the time frame of their chronic disease.
Guidelines as Topic↗
Organ preservation solutions in heart transplantation--patterns of usage and related survival.
Despite experimental advantages for certain heart preservation solutions (HPS), their clinical popularity and related survival are uncertain. We surveyed all active UNOS heart transplant centers to determine their HPS. HPS survival benefits were tested using the UNOS heart transplant registry. Centers used from 1 to 3 types of 167 solutions. Of these formulations, 55.1% were commonly cited solutions. The other (custom) mixtures differed from those usually reported. All solutions were classified as intracellular (I, [Na++] < 70 mEq/L) or extracellular (E, [Na++] > or = 70 mEq/L). Significant variations in solution usage were observed among major regions of U.S. transplant activity (Northeast [NE], Southeast [SE], and West [W], P < 0.001). For example, 62.5% of University of Wisconsin (UW) and 49.3% of "Other" usage occurred in the NE; 75% of Roe and 100% of Collins usage occurred in the SE; and 100% of Krebs and 46% of Stanford usage occurred in the W. Logistic regression analyses of 9401 patients who underwent transplantation from 10/87 to 12/92 showed a reduction in the adjusted one month mortality odds ratio for grafts preserved with I rather than E solutions (0.85, P < 0.05). Compared with the most commonly used solution, Plegisol (20.1% of cases), the following adjusted odds ratios for one-month mortality were observed: UW, 1.09 (ns); Stanford, 0.80 (P < 0.10); Roe, 0.36 (P < 0.001); Collins, 0.82 (ns); Krebs, 0.14 (P < 0.01). Using the same one month comparison with Plegisol, 16.8% of grafts that received Custom-I solutions also fared better (0.75, P < 0.05) than the 21.4% that had Custom-E mixtures (0.91, ns). HPS usage varies greatly and there are regional preferences. There may be early survival benefits for certain intracellular HPS--however, further study is warranted to explore such relationships.
Cardioplegic Solutions↗
Feasibility of mathematical models to predict success in video-assisted thoracic surgery lung nodule excision.
BACKGROUND: Pulmonary nodules are occasionally difficult to excise using video-assisted thoracic surgery (VATS). METHODS: To predict operative success, mathematical models using preoperative computerized tomography (CT) measurements were tested in 50 consecutive patients who underwent attempted or successful thoracoscopic lung biopsy. Unrelated technical problems resulted in the exclusion of 3 patients. RESULTS: No differences were noted with respect to lobar location, thoracic dimensions, gender, presence of chronic obstructive pulmonary disease, or nodule pathology. The expression S/(D + 1), where S = nodule size (cm) and D = distance (cm) to the nearest visceral pleura, yielded significantly higher values for visible nodules (P < 0.001). Resectable nodules had a higher score using the expression 1/(S + D + 1), (P < 0.001). Simple cases (n = 19) were defined as those in which nodules were both visible and resectable with very basic VATS techniques. All others (n = 28) were considered complex. The derived expression for Simplicity [1/(S(D + 1))] yielded significantly higher values for simple cases (0.8 +/- 0.3 vs. 0.3 +/- 0.2 cm(-2), P < 0.001) and all simple cases had a score > or = 0.4. Logistic regression analysis showed that the formulas for resectability and simplicity were significant independent predictors for resectability and simplicity. CONCLUSIONS: Equations based on objective CT measurements may be useful for planning VATS nodulectomy or studying the outcome of these minimally invasive operations.
Feasibility Studies↗
The living donor process in kidney transplantation: influence of race and comorbidity.
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Alabama↗
Renal transplantation in African-American recipients: three decades at a single center.
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Adult↗
The impact of renal transplantation on survival in hepatitis C-positive end-stage renal disease patients.
Hepatitis C virus (HCV) infection is common in end-stage renal failure patients. It is not known whether the prognosis of HCV-positive patients differs depending on whether they remain on dialysis or receive a kidney transplant. To address this question, we compared the outcomes of HCV-positive renal transplant recipients and HCV-positive patients who were acceptable candidates but had not yet received transplants. We reviewed all patients referred to our institution for renal transplantation evaluation between January 1992 and December 1995. Anti-HCV antibody was detected in 151 of 2,053 (7.4%) patients. HCV-positive patients were more often male (74% v 56%; P < 0.0001), black (68% v 49%; P = 0.001), unemployed (87% v 74%; P = 0.0004), on dialysis (88% v 78%; P = 0.0026), and on dialysis longer (30 +/- 44 months v 13 +/- 23 months; P = 0.0001) than HCV-negative patients. We determined the outcomes of HCV-positive patients who had at least 2 years' follow-up. Thirty-three HCV-positive patients received kidney transplants (group I); 25 HCV-positive patients were acceptable transplant candidates but had not yet received an allograft (group II). Group I and II HCV-positive patients were similar with respect to age, race, duration of dialysis, cause of renal failure, prevalence of heart disease, and results of liver function tests. Survival was significantly decreased in group II versus group I (P = 0.043). Our study showed that HCV-positive renal transplant recipients had a better survival than similar HCV-positive patients awaiting transplantation.
Adult↗
Treatment of hypertension in renal allograft patients: does drug selection make a difference?
Recent trials have suggested that control of mild to moderate hypertension can slow progression of many forms of chronic renal disease. These findings may apply to renal transplant hypertension. Renal transplant hypertension, however, does not always behave like other forms of hypertension. Thus, clinical trials have not yet shown that blood pressure control will alter the progression of "chronic rejection." What's more, which of the classes of antihypertensive agents might be most effective is also not certain. Most trials suggest that calcium inhibitors and angiotensin-converting enzyme inhibitors have similar effects on blood pressure and glomerular filtration rate in hypertensive transplant patients.
Antihypertensive Agents↗
Differential gene expression of extracellular matrix components in dilated cardiomyopathy.
Extracellular matrix metalloproteinases (MMPs) are activated in dilated cardiomyopathic (DCM) hearts [Tyagi et al. (1996): Mol Cell Biochem 155:13-21]. To examine whether the MMP activation is occurring at the gene expression level, we performed differential display mRNA analysis on tissue from six dilated cardiomyopathy (DCM) explanted and five normal human hearts. Specifically, we identified three genes to be induced and several other genes to be repressed following DCM. Southern blot analysis of isolated cDNA using a collagenase cDNA probe indicated that one of the genes induced during DCM was interstitial collagenase (MMP-1). Northern blot analysis using MMP-1 cDNA probe indicated that MMP-1 was induced three- to fourfold in the DCM heart as compared to normal tissue. To analyze posttranslational expression of MMP and tissue inhibitor of matrix metalloproteinase (TIMP) we performed immunoblot, immunoassay, and substrate zymographic assays. TIMP-1 and MMP-1 levels were 37 +/- 8 ng/mg and 9 +/- 2 ng/mg in normal tissue specimens (P < 0.01) and 2 +/- 1 ng/mg and 45 +/- 11 ng/mg in DCM tissue (P < 0.01), respectively. Zymographic analysis demonstrated lytic bands at 66 kDa and 54 kDa in DCM tissue as compared to one band at 66 kDa in normal tissue. Incubation of zymographic gel with metal chelator (phenanthroline) abolished both bands suggesting activation of neutral MMP in DCM heart tissue. TIMP-1 was repressed approximately twentyfold in DCM hearts when compared with normal heart tissue. In situ immunolabeling of MMP-1 indicated phenotypic differences in the fibroblast cells isolated from the DCM heart as compared to normal heart. These results suggest disruption in the balance of myopathic-fibroblast cell ECM-proteinase and antiproteinase in ECM remodeling which is followed by dilated cardiomyopathy.
Blotting, Northern↗
Impact of donor/recipient size matching on outcomes in renal transplantation.
Interest in nonimmunologic factors affecting longterm graft survival has focused on adequacy of nephron dosing. Body surface are (BSA) is a reliable surrogate for nephron mass. In a retrospective study of 378 primary recipients of paired kidneys from 189 cadaveric donors, we assessed the impact of matching donor and recipient BSA on outcome over 7 years. BSA of donors was 1.82 +/- 0.26 m2. Initially, paired recipients of kidneys from a single donor were divided into two groups. Group 1 included the recipient with the larger BSA of the pair (1.97 +/- 0.17 m2), while group 2 consisted of smaller BSA recipients (1.69 +/- 0.19 m2). Although early function was better in group 2 patients, graft survival at 1 year (77% vs. 79%) and 5 years (54% vs. 55%) was identical between groups, as were most recent serum creatinine levels (2.0 +/- 0.1 vs. 2.1 +/- 0.1 mg/dl). A second analysis divided patients with a functioning allograft at discharge from initial transplant hospitalization (n = 345) into three groups based solely on donor to recipient BSA ratio: the ratio of group A (n = 30) was < or = 0.8, that of group B (n = 255) was between 0.81 and 1.19, and that of group C (n = 51) was > or = 1.2. Graft survival and kidney function over 5 years did not differ among groups. In multivariate analysis of 17 variables, donor:recipient BSA, independent of other risk factors, did not affect risk allograft loss. These data indicate that including nephron mass as a criterion for cadaveric organ allocation is unlikely to improve long-term results in renal transplantation.
Adult↗
Post-transcriptional regulation of extracellular matrix metalloproteinase in human heart end-stage failure secondary to ischemic cardiomyopathy.
Human heart matrix metalloproteinases (MMP) are present in the latent form and activated in the failing heart. To examine whether the MMP activation was due to gene and/or post-translational modification, we analysed tissue from 10 explanted hearts due to coronary heart disease (CHD) and five normal left atrial tissue from donor hearts. Based on in situ immunolabeling MMP-1, tissue inhibitor of metalloproteinase (TIMP-1) and collagen were co-localized in the interstitial tissue. Based on sandwich ELISA, TIMP-1 and MMP-1 levels were 37 +/- 8 ng/mg and 9 +/- 2 ng/mg in normal tissue (P < 0.01) and 12 +/- 5 ng/mg and 75 +/- 11 ng/mg in the infarcted tissue (P < 0.01), respectively. These levels suggest repression of TIMP-1 during myocardial infarction. Northern blot analysis indicated that the mRNAs for both MMP-1 and TIMP-1 were increased three-to four-fold in the infarcted tissue as compared to the normal tissue, suggesting upregulation of MMP and TIMP gene transcription following infarction. Based on in situ tissue overlay zymography, the generalized activation of MMP was observed in the interstitium of the infarcted heart. Zymographic and immunoblot analysis demonstrated the presence of one band at 66 kDa (MMP-2) in the normal tissue and several bands at 92 (MMP-9), 66 (MMP-2) and 54 kDa (MMP-1) in the infarcted heart. Incubation of the zymographic gel with metal chelator (phenanthroline) abolished bands at 92 kDa and 54 kDa but phenanthroline did not abolish the lytic band at 66 kDa. The 66 kDa band was completely abolished in the presence of phenanthroline and phenyl methyl sulfonyl fluoride (PMSF). 2D-zymographic analysis suggested that the lytic band at 66 kDa was a mixture of two neutral proteinases with different isoelectric point. Plasminogen/gelatin zymographic analysis of infarcted tissue extract indicated that the band at 66 kDa was plasmin generated due to increased expression of tissue plasminogen activator (tPA) activity. In relation to increased expression of gelatinase in the infarcted tissue, our data suggest that gelatinase B (92 kDa) is induced in diseased heart. The results suggest that tPA converts plasminogen to plasmin which, in turn, activates MMPs and inactivates TIMP-1 post-translationally following ischemic cardiomyopathy.
Cardiomyopathies↗
Use of centrifugal pumps for postcardiotomy ventricular failure: technique and anticoagulation.
BACKGROUND: Centrifugal pumps have been employed most commonly for postcardiotomy mechanical support after intraaortic balloon pumping has failed. Despite their effectiveness in some patients, morbidity remains high. METHODS: Our clinical experiences with centrifugal pumps were reviewed with particular attention to common morbidity such as bleeding, coagulopathy, and thromboembolism. Evolution of cannulation techniques and anticoagulation strategies were defined. Morbidity during early and more recent experience was compared. RESULTS: Deranged coagulation and excessive mediastinal bleeding were commonly observed in patients undergoing centrifugal mechanical assist for postcardiotomy cardiogenic shock. Evolved strategies to reduce blood loss included meticulous cannulation techniques, early use of blood components, and an aggressive policy of mediastinal reexploration. Thromboembolism occurred with centrifugal mechanical assist, was underestimated by clinical events, and dictated pursuit of improved anticoagulation strategies and device refinement. A clinically significant trend of decreasing morbidity from early to recent experience was observed. CONCLUSIONS: Increasing clinical experience with centrifugal mechanical assist appears to result in a clinically relevant decrease in morbidity.
Anticoagulants↗
Dilemmas in renal transplantation: when the clinical course and histological findings differ.
Histological examination of renal allograft tissue has become the accepted standard in diagnosing acute rejection. We present three cases of allograft dysfunction in which the histological findings and clinical course differed. Reliance on histology alone in therapeutic decision making might have resulted in inappropriate clinical interventions. In renal transplantation, biopsy results must always be interpreted in conjunction with clinical findings.
Adult↗
Benefits of continued cyclosporine through an indigent drug program.
Financial circumstances force some stable renal transplant recipients to discontinue cyclosporine (CsA). Previous results from our center document a subgroup of these patients at increased risk for acute rejection and allograft loss, namely, those of African ancestry. After 1988, such disadvantaged recipients have been able to receive CsA at no charge through the National Organization for Rare Disorders (NORD). At the University of Alabama at Birmingham, 54 patients were enrolled in the NORD program between 1988 and 1994. Acute rejection, allograft survival, and patient survival in these patients were compared with those in 42 patients who, prior to 1988, were withdrawn from CsA for financial reasons. Both groups were similar socioeconomically. The mean follow-up was 69 +/- 33 months (+/-SD) in the withdrawal group and 45 +/- 14 months in those entering the NORD program. Acute rejections occurred with similar frequency in both groups before CsA withdrawal (45%) or NORD enrollment (48%). In contrast, acute rejections were more common in patients after the onset of CsA withdrawal (38%) than after NORD enrollment (11%) (P < 0.01). Black patients withdrawn from CsA experienced more acute rejections than their counterparts in the NORD program (57% v 15%) (P < 0.01). White NORD recipients also experienced fewer acute rejections, although the difference was not statistically significant (withdrawal group 16% v NORD group 4%; P = 0.29). Rejection episodes were accompanied by reduced graft survival in black patients withdrawn from CsA, while significant improvement was seen in those remaining on CsA-based therapy (P < 0.05). No difference in allograft survival was seen among white patients in either group (withdrawal group 74% v NORD group 82%; P = 0.33). Thus, long-term access to CsA through the NORD program reduced acute rejections and improved allograft survival in an economically disadvantaged subgroup of renal transplant recipients. These findings emphasize the importance of continued access to CsA in black renal transplant recipients and its influence on long-term allograft survival.
Acute Disease↗
Amlodipine increases cyclosporine levels in hypertensive renal transplant patients: results of a prospective study.
Calcium channel blockers (CCB) are considered the agents of choice to treat hypertension in cyclosporine (CsA)-treated renal transplant patients. Verapamil, diltiazem, and nicardipine, but not nifedipine or isradipine, can significantly increase CsA levels. The effect of a new CCB, amlodipine, has not been established. However, some hospitals are routinely switching patients to amlodipine from other CCB for reasons of cost. A case of a man with stable CsA levels who developed significantly increased CsA levels after being changed to amlodipine is presented along with a prospective trial to formally examine this issue. Eleven hypertensive, CsA-treated renal transplant patients were placed on amlodipine for an average of 6.9 wk and later withdrawn. Three measurements of CsA trough level, blood pressure, serum creatinine concentration, and BUN were obtained at baseline, during treatment with amlodipine, and after withdrawal of amlodipine. CsA levels on amlodipine increased an average of 40% above baseline (P = 0.003) and decreased to baseline (P = 0.001) after amlodipine was withdrawn, despite no significant change in CsA dose. Additionally, there was no change in serum creatinine, BUN, or mean arterial pressure values. Amlodipine can increase CsA levels
Adult↗