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Biomedical subjects

S M Flechner

Publications and source records attributed to S M Flechner.

At least 73 records · Page 4Linked to original sources
PubMed1986

Analysis of pharmacokinetic profiles in 232 renal and 87 cardiac allograft recipients treated with cyclosporine.

Analyses of cyclosporine (CsA)-related compounds (Cs) using the radioimmunoassay method were performed by 232 profiles in renal and 87 profiles in cardiac allograft recipients. Cardiac allograft recipients tended to have an increased, dose-corrected area under the concentration (AUC) v time curves after oral and, particularly, intravenous CsA administration, to display a slower drug clearance rate, and to have a slightly smaller volume of distribution. The impact of age, sex, hepatic impairment, nephrotoxicity, and concomitant corticosteroid dose could be discerned within the large number of studies in renal recipients. Only nephrotoxic cardiac transplant patients showed a significant alteration of increased AUC:dose and drug half-life compared with patients with normal renal function, a similar change to that observed in nephrotoxic renal transplant patients. Pediatric compared with adult renal recipients showed a threefold increased rate of mean drug clearance, namely 39.6 mL/min/kg in children v 12.3 mL/min/kg in adults, which may explain the almost 50% reduction in area under the plasma concentration curve v the time curve. There also appeared to be somewhat better oral absorption of CsA by children. Study of greater numbers of cardiac transplant recipients will be necessary to detect the subtle impact of demographic factors on pharmacokinetic parameters.

Adult↗
PubMed1985

Does cyclosporine influence the results of cadaver retransplantation?

The results of cadaveric retransplantation in 55 recipients immunosuppressed with cyclosporine and prednisone were compared to 156 recipients of primary renal allografts. By 3 yr posttransplant, there is no significant difference in patient survival, but the yearly graft survival for primary (79%, 72%, 72%) as compared to retransplant (69%, 58%, 58%) recipients was significantly (p less than 0.05) better. There was no significant difference in rejection episodes or mean +/- SD serum creatinine (mg/dl) at 2 yr between primary (32%, 2.14 +/- 1.1) and retransplant (33%, 2.08 +/- 1.4) patients, respectively. Donor source, third kidneys, human leukocyte antigen AB and Dr matching, percent reactive antibody levels, and cause of first graft loss do not have significant impact on cyclosporine-treated retransplant outcome. However, retransplant patients who have lost a previous graft in less than 3 months continue to be at high risk for subsequent early graft loss. These results suggest that the combination of cyclosporine and prednisone is the preferred regimen for cadaveric retransplantation.

Antibody-Dependent Cell Cytotoxicity↗
PubMed1985

Use of cyclosporine in pediatric renal transplant recipients.

Cyclosporine and prednisone were used in combination to produce immunosuppression in 18 pediatric recipients of renal allografts. Ten children received cadaveric kidneys and eight received kidneys from living related donors. With a mean follow-up of 16.5 months (range 7 to 33 months), the patient survival rate is 100% (18 of 18) and the graft survival rate is 83% (15 of 18). Two grafts were lost for nonimmunologic reasons. Currently the group mean (+/- SE) serum creatinine concentration is 1.22 +/- 0.11 mg/dl and creatinine clearance is 69.3 +/- 4.79 ml/min/1.73 m2. Cyclosporine nephrotoxicity has not caused irreversible allograft injury nor led to graft loss in this population. The incidence of treated rejection episodes has been 39% (seven of 18). Only 39% (seven of 18) of children have required hospital readmissions since the initial transplant discharge. There have been no opportunistic infections. In the 15 children with functioning grafts, some linear growth has occurred in 10 of 11 prepubertal and two of four postpubertal patients. Cyclosporine and prednisone have constituted a safe, efficacious immunosuppressive regimen for pediatric renal allograft recipients. Longer follow-up will be necessary to confirm whether these advantages persist beyond 2 years.

Adolescent↗
PubMed1985

Salvage of difficult transplant complications by percutaneous techniques.

The use of percutaneous endourological techniques is demonstrated in recipients of renal allografts. Transplant complications that previously had required prompt surgical intervention may be approached safely by the judicious use of percutaneous manipulations. While examples of perirenal hematoma, renal abscess, urinary fistula and renal pelvic stone extraction are presented, close patient observation and a low threshold for surgical intervention are recommended to permit the continued, safe evaluation of this approach.

Adult↗
PubMed1985

The presence of cyclosporine in body tissues and fluids during pregnancy.

A term pregnancy, labor, and delivery is reported in a cyclosporine- and prednisone-treated female cadaveric renal allograft recipient. A male child, small for gestational age at 2370 g, was born at 38 weeks of gestation with neither congenital anomalies nor nephrotoxicity or hepatotoxicity. Cyclosporine (CSA) concentrations as determined by a radioimmunoassay are reported in maternal and fetal tissues. CSA is present in the fetal circulation during gestation at similar concentrations to those in the mother. Fetal serum at birth displayed 25% suppression of a third-party mixed lymphocyte culture (MLC) compared with control incubations. CSA was present in maternal breast milk; therefore, breastfeeding of children by CSA-treated mothers should be avoided.

Adult↗
PubMed1985

Impact of cyclosporine on renal transplant practice at the University of Texas Medical School at Houston.

CsA has improved the outcome of renal allotransplantation with CAD and LRD kidneys. CsA mitigates risk factors heretofore presenting substantial obstacles to CAD transplantation: HLA matching, pretransplant splenectomy, extensive numbers of conditioning blood transfusions, and old age. In LRD transplantation, CsA obviates the need for donor-specific transfusions in the haploidentical situation, and for prednisone in the HLA-identical setting. The incidence of drug-induced nephrotoxicity beyond six months is 30% with the degree of dysfunction proportionate to the degree of histo-incompatibility, suggesting that subclinical allograft rejection due to overzealous dose reduction may compromise allograft function. At present, total conversion from CsA to Aza appears ill-advised; even patients who never suffered allograft rejection under CsA therapy frequently lose their allograft when the inferior level of Aza suppression is substituted. Drug-induced hypertension, a modestly significant factor, diminishes further by two years posttransplant. The benefit of CsA therapy is a reduced incidence of 19% initial and 10% recurrent rejection episodes. Of great importance is the observation that 17% of rejection episodes followed patient noncompliance. Further, the incidence of bacterial infections was greatly reduced, and viral infections modestly lessened. Only the occurrence of pneumocystis carinii was increased, but 92% of patients survived in spite of serious pulmonary infection. Development of a consistent CsA regimen has reduced the median initial hospitalization to 12.5 days for LRD and 14 days for CAD, a level well within the range stipulated for the Disease-Related Guidelines of the Medicare Program. Furthermore, readmission is less frequent; one-third of patients never reenter the hospital.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1985

Successful transplantation of cyclosporine-treated allograft recipients with serologically positive historical, but negative preoperative, donor crossmatches.

Eighteen renal allograft recipients (15 cadaveric and 3 haploidentical living-related donor transplants) with historically (Hx)3 positive, but pretransplant (pre-Tx) negative, donor crossmatches (XM) were treated postoperatively with cyclosporine (CsA) and prednisone (Pred). The one-year allograft survival for the 14 primary allograft recipients was 86% (12/14). This was comparable to, and not significantly different from, the 81% (51/63) graft survival for recipients of primary cadaveric donor allografts transplanted during the same period who displayed a negative donor crossmatch with both Hx and pre-Tx sera. All four retransplant recipients with (+) Hx, but (-) pre-Tx, donor Xms lost their grafts. This result was significantly different (P less than 0.05) from the 75% (27/36) graft survival for retransplant recipients displaying a negative donor crossmatch with both Hx and pre-Tx sera. A significant decrease in PRA of 52 +/- 19% to 19 +/- 16%, P less than 0.05, was displayed by 12/18 CsA patients when comparing (+) Hx to (-) pre-Tx sera, which could have influenced the allograft survival in those patients. However, a graft survival of 44% (4/9) was observed for azathioprine (Aza) and Pred-treated recipients of cadaveric donor renal allografts who also displayed a significant decrease in PRA of 50 +/- 22% to 5 +/- 4%, P less than 0.05 when comparing Hx to pre-Tx sera. The decreasing PRA did not beneficially affect these Aza-Pred patients' graft survival. Therefore, CsA-Pred afforded a beneficial effect when recipients of a primary cadaveric renal allograft displaying a (+) Hx, but (-) pre-Tx, XM were transplanted. Retransplant recipients, however, should receive a cadaveric donor allograft only when they are XM-unreactive, whether testing with pre-Tx or Hx sera.

ABO Blood-Group System↗
PubMed1985

100 living-related kidney donor evaluations using digital subtraction angiography.

Intravenous digital subtraction angiography (IV-DSA) combined with excretory urography was used to evaluate the renal anatomy of 100 potential living-related kidney donors. Each of the 100 patients underwent subsequent nephrectomy to verify the number and distribution of renal vessels. For the entire series, 71 patients had bilateral single, 2 bilateral multiple and 27 multiple renal arteries on one side determined by angiography. Eleven patients required standard catheter angiography due to inadequate IV-DSA studies. Four patients who had a single artery imaged by IV-DSA were found to have an additional vessel at the operation. The overall accuracy of IV-DSA to identify the number of renal vessels was 96% (85/89). The sensitivity of the exam was 100% (94/94) and the specificity was 67% (4/6). It is concluded that IV-DSA combined with excretory urography is a safe, cost effective, and suitable method to image the renal anatomy of potential kidney donors. Thus about 90% of donors can be spared the risks and inconvenience of standard angiography, and the donor evaluation can now be performed on an outpatient basis.

Adult↗
PubMed1985

De novo hemolytic uremic syndrome in renal transplant recipients immunosuppressed with cyclosporine.

Three renal transplant recipients were studied who developed the hemolytic uremic syndrome (HUS) during cyclosporine (CsA) immunosuppression. All patients displayed characteristic findings including normocytic, normochromic anemia, thrombocytopenia, erythrocyte morphologic abnormalities, increased numbers of reticulocytes, bone marrow hyperplasia, and renal failure. The clinical studies support the diagnosis of an extrinsic hemolytic process. Renal biopsy specimens demonstrated fibrin deposition and glomerular thrombosis. The renal failure was not responsive to antirejection therapy. The first patient was converted to azathioprine and consequently had a gradual improvement in renal function. Failure to convert the second patient resulted in adequate immunosuppression and subsequent graft loss. The third patient's improvement corresponded with a moderate CsA dose reduction. The occurrence of HUS in these patients represents a de novo presentation after CsA immunosuppression. An analysis of these cases indicates that CsA should be discontinued if HUS persists after moderate dose reduction.

Adult↗
PubMed1984

Acute cellular rejection or Cyclosporine A nephrotoxicity? A review of transplant renal biopsies.

Cyclosporine (CsA), a powerful immunosuppressive agent that increases graft survival in renal transplant recipients, is often nephrotoxic. The clinical distinction between acute rejection and CsA nephrotoxicity (NT) is a common challenge in the management of these patients. To seek a histologic distinction between acute rejection and CsA-NT, we reviewed the renal biopsies performed prior to initiation of therapy for rejection or nephrotoxicity in two groups of patients. Group 1 (ten patients) had criteria consistent with acute rejection and responded to steroid pulse therapy. Group 2 (15 patients) was treated for CsA-NT and responded to a decrease in the dose of CsA. We conclude that CsA-NT has no specific histologic features. A prominent interstitial mononuclear cell infiltrate as well as tubulitis are features of acute cellular rejection. These findings do not exclude the possibility that rejection and CsA-NT can co-exist in the same patient.

Biopsy↗
PubMed1984

Successful transplantation of cyclosporine-treated haploidentical living-related renal recipients without blood transfusions.

A protocol of cyclosporine and prednisone immunosuppression was used in 36 consecutive haploidentical living-related renal transplant recipients from donors displaying marked proliferation in mixed lymphocyte culture (MLC) reactions. All blood transfusions (random third-party and donor-specific) were withheld once a negative crossmatch with the prospective kidney donor was obtained. With a mean follow-up of 13.6 months, patient survival is 97% (35/36) and graft survival is 92% (33/36). One graft was lost to rejection; two were abandoned because of sepsis. Only 14% (5/36) of patients experienced a rejection episode. No significant differences were evident in graft survival, rejection episodes, or renal function between the 15 recipients who were never transfused and the 21 with a history of previous blood transfusions. These findings suggest that pretransplant blood transfusions not only are unnecessary to achieve excellent graft survival, but also may jeopardize donor availability by donor-specific presensitization.

Adolescent↗
PubMed1984

The use of cyclosporine in living-related renal transplantation. Donor-specific hyporesponsiveness and steroid withdrawal.

Fourteen HLA-identical (HLA-ID) and 62 haploidentical (HP-ID) living-related donor (LRD) renal allograft recipients were transplanted using cyclosporine (CsA) and prednisone immunosuppression. No patients were preconditioned with pretransplant blood transfusions (third-party or donor-specific)--and, therefore, none were sensitized to their donor. Patient 93% (13/14) and graft 93% (13/14) survival for the HLA-ID patients is not significantly different (P greater than .1) compared with patient 98% (61/62) and graft 91% (56/62) survival in the HP-ID patients, with a mean follow-up of 16.3 (8-30) and 14.7 (2-35) months, respectively. A significant difference was noted in the incidence of treated rejection episodes (0% vs. 31%, P less than .01) and the mean serum (mg/dl) creatinine (1.37 vs. 1.71, P less than .05) at 18 months between the HLA-ID and the HP-ID and HP-ID recipients, respectively. Ten of 22 HP-ID recipients demonstrated donor-specific mixed lymphocyte culture hyporesponsiveness one year posttransplant that may have been due to the emergence of monocytoid suppressor cells. Nine of these HP-ID and seven HLA-ID recipients were subjected to a protocol of steroid withdrawal. Eleven of these patients are currently on CsA monodrug therapy and two are on alternate-day steroids from 9-18 months after discontinuation of prednisone. These findings suggest that CsA is an effective steroid-sparing agent in LRD renal transplantation that diminishes the frequency of treated rejection episodes and may permit monodrug therapy in selected individuals.

Adult↗