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Biomedical subjects

S M Flechner

Publications and source records attributed to S M Flechner.

At least 37 records · Page 2Linked to original sources
PubMed1997

The use of kidneys from living donors with renal vascular disease: expanding the donor pool.

PURPOSE: The disparity between the number of patients awaiting organ transplantation and the number of available donor organs continues to increase. We report the outcomes of transplantation using kidneys from living donors who had unilateral renovascular disease. MATERIALS AND METHODS: We identified 5 living donors who had unilateral renovascular disease, including saccular renal artery aneurysms, an arteriovenous malformation, localized atherosclerosis and fibromuscular renal artery stenosis. Each donor was normotensive and asymptomatic, and had otherwise normal renal function. RESULTS: In each case the abnormal kidney was removed, the lesion was repaired ex vivo and the kidney was successfully transplanted without complication in the donor or recipient. Each recipient had a serum creatinine of less than 2 mg./dl. and each donor remained normotensive with stable renal function at up to 3 years of followup. CONCLUSIONS: Kidneys from living donors with renovascular disease can be transplanted safely provided that careful selection, informed consent and a normal remaining kidney are ensured.

Adult↗
PubMed1997

The current level of involvement of urological trainees and faculty in clinical kidney transplantation in the United States and Canada.

PURPOSE: We attempted to quantitate the level of participation of urology residents and faculty in clinical renal transplantation in the United States and Canada at the present time. MATERIALS AND METHODS: All 123 urology residency program directors in the United States and all 13 in Canada were mailed a questionnaire requesting information about the participation of their residents and faculty in clinical renal transplantation at their institutions. All program directors (100%) returned the surveys. RESULTS: In the United States 94% of residencies are affiliated with renal transplant programs and 81% provide a transplant rotation. In Canada each program provides a transplant experience. In the United States 22% and in Canada 85% of academic renal transplant programs are directed or codirected by urology. In the United States approximately 80% and in Canada more than 90% of residents are exposed to transplant surgery, although the majority have pre-urology or junior resident rotations. Approximately 50% of residents in each country receive training in immunosuppression. In the United States 25% of programs have urology faculty perform transplant surgery and administer immunosuppression, compared to more than 90 and only 15%, respectively, in Canada. CONCLUSIONS: Urological participation in clinical renal transplantation at academic medical centers remains strong with approximately 25% of programs directed or codirected by urology departments in the United States--a figure that has not changed appreciably during the last 10 years. In the future the continued presence of urology in transplantation requires a commitment from urology program directors to support exposure for residents as well as promoting the training and development of young transplant surgeons within our own specialty.

Canada↗
PubMed1996

Determinants of chronic renal allograft rejection in cyclosporine-treated recipients.

We analyzed the development of chronic rejection in 511 kidney-only renal transplants in 507 patients between July 1987 and November 1994. A database was established for recipients > or = 18 years old who received cyclosporine-based immunosuppression and demonstrated graft survival for a minimum of 12 months. The 347 recipients of cadaver transplants (67.9%) and 164 recipients of live donor transplants (32.1%) were followed for 12 to 102 months (mean 51 months). Chronic rejection was diagnosed in 124 transplants (24%), with a mean time to diagnosis of 23+/-18 months (range 3-92). Risk factors were identified in a multivariate analysis using the Cox model. The impact of the timing and severity of rejection episodes was analyzed in a univariate model. The presence of chronic rejection resulted in decreased (P=0.0001) 5-year graft survival for both cadaver graft (83.7% vs. 58.2%) and live donor graft (93.2% vs. 53.1%) recipients. Significant variables for the development of chronic rejection included an acute rejection episode (P=0.0001), a black recipient (P=0.0006), donor age > or = 50 years (P=0.006), and a serum creatinine level >2.0 mg/dl by 6 months after transplantation. Severity of rejection measured by peak serum creatinine or posttreatment return to baseline was not related to chronic rejection. However, acute rejection episodes lasting for more that 5 days (P=0.03) or occurring after 6 months (P=0.001) did influence time to chronic rejection. In addition, mismatching for donor-recipient race was a significant (P=0.008) risk factor for recipients of cadaver grafts. We conclude that acute rejection is the most significant risk factor for chronic rejection, and the long-term fate of grafts may be determined as early as the first 6 months. Racial matching of donor-recipient pairs may be useful to minimize chronic rejection risk. Future advances that diminish the incidence and severity of acute rejection may have the greatest impact on long-term survival.

Acute Disease↗
PubMed1996

Long-term follow-up of kidneys transplanted from elderly cadaveric donors.

This report examines the long-term results obtained in 50 patients transplanted between 1977 and 1990 with kidneys from cadaveric donors aged 55-70 (median 59) years. The recipients comprised 27 men and 23 women aged 8-68 (median 42) years. In all, 20 patients (40%) had end-stage renal disease on the basis of glomerulonephritis, whereas 8 (16%) were diabetic. Immunosuppression was induced with antilymphocyte globulin and maintained with azathioprine and prednisone in all patients in addition to cyclosporine in the 35 patients transplanted since 1985. Immediate graft function occurred in 18 patients (36%), and 36 patients (72%) were off dialysis at 1 year posttransplant. Altogether, 25 patients (50%) had functioning grafts at 5 years posttransplant, and at up to 13 years of follow-up (mean 5.8 years), 22 patients (44%) are off dialysis and their serum creatinine levels range from 0.8 to 3.8 mg/dl (mean 2.0 mg/dl). In all, 12 patients (24%) expired from 2 months to 15.5 years posttransplant (mean 4.3 years), and 5 of these patients died with functioning grafts. These 5 deceased recipients and the 22 who remain alive with functioning grafts had a mean antigen match of 2.27 with their donors. The other 23 patients whose grafts failed had a mean antigen match of 2.13 (P = 0.77). The 15 recipients who were transplanted prior to the cyclosporine era had lower 1- and 5-year allograft survival rates of 67% and 47%, respectively, as compared with their counterparts, who took cyclosporine-based immunosuppression (74% and 51%, P = 0.58 and 0.76, respectively). Likewise, the 32 recipients with delayed graft function had lower 1- and 5-year allograft survival rates of 66% and 47%, respectively, as compared with the group with immediate graft function (83% and 56%, P = 0.18 and 0.56, respectively). We conclude that acceptable long-term patient and graft survival may be achieved by transplanting these organs and that the degree of HLA matching does not affect their outcome significantly. Patients with immediate allograft function also tended to do better over the long term. Although cyclosporine-based immunosuppression was advantageous within 1 year of transplant, its beneficial effect was less marked 5 years out.

Adolescent↗
PubMed1996

Testicular seminoma originating in an undescended testis in a renal allograft recipient.

Immunosuppressed transplant recipients are at significantly increased risk for developing neoplasms than are nonimmunosuppressed individuals. However, only six cases of pure testicular seminoma following renal transplantation have been reported in the English literature. This case report represents the first description of a seminoma arising in an undescended testis post-transplantation. We propose that it may be prudent to remove atrophic undescended testes when lifelong immunosuppressive therapy is anticipated, because accelerated tumor growth can occur.

Adult↗
PubMed1996

Transplantation into the long-term defunctionalized bladder.

PURPOSE: We evaluated the outcome of transplantation into a long-term defunctionalized bladder. MATERIALS AND METHODS: Since 1985 we performed transplantation in 5 dialysis dependent patients after excision of the ileal conduit and native kidneys. The bladder was evaluated before transplantation with cystoscopy, voiding cystography, urodynamics and demonstration of continence. Bladder rehabilitation was accomplished by cycling through a suprapubic tube or urethral catheter, and no bladder augmentation was done. All patients received antibiotic prophylaxis for several years. RESULTS: Five male recipients underwent transplantation at ages 22, 29, 30, 31 and 55 years, and they had had a defunctionalized bladder for 15, 17, 23, 25 and 26 years. All patients were alive with a functioning allograft at 6, 84, 90, 112 and 120 months after transplantation. Current serum creatinine values are 1.2, 1.6, 1.8, 2.3 and 2.5 mg./dl. Median urodynamic values before and after transplantation were bladder capacity 60 and 300 cc, respectively, peak flow rate 5 and 18 cc per second, respectively, and post-void residual 20 and 15 cc, respectively. One patient required self-catheterization. CONCLUSIONS: Renal transplantation into a long-term defunctionalized bladder can be performed safely in carefully selected patients. Bladder function and continence should be confirmed before transplantation using a program of progressive bladder rehabilitation.

Adult↗
PubMed1994

Current status of renal transplantation. Patient selection, results, and immunosuppression.

Renal transplantation is now well accepted as the preferred mode of renal replacement therapy for patients with end-stage renal disease. Recent advances in surgery, anesthesia, immunosuppression, and antimicrobial prophylaxis have made transplantation a more predictable clinical activity. The demand for kidneys has far outstripped the available supply in the United States, and careful selection and preparation of recipients is required to maximize the effective use of this limited resource. Newer immunosuppressive agents are on the horizon that offer promise for a further reduction in allograft rejection and decrease in post-transplant complications.

Contraindications↗
PubMed1992

Arithmetic versus harmonic mean values for cyclosporin-A pharmacokinetic parameters.

The harmonic and arithmetic mean values for volume of distribution at steady state, half-life, and clearance of intravenous cyclosporin-A were calculated using an index set of 22 renal transplant candidates to determine if harmonic mean values provide a less biased estimate of central tendency than arithmetic mean values. Cyclosporin-A was measured using a nonspecific radioimmune assay method. The arithmetic mean value for volume of distribution was 16% larger than calculations by the harmonic mean method. Similarly, the arithmetic mean half-life and clearance values were larger than harmonic mean values by 10% and 15%, respectively. However, 95% confidence intervals for these pharmacokinetic parameters overlapped. When these mean pharmacokinetic parameter values were used to predict actual values in a test group of 22 renal transplant candidates receiving cyclosporin-A, similar levels of precision were demonstrated by either method. Both methods produced positively biased predictions for volume of distribution and clearance. However, these differences were not significant. These findings suggest there is little practical value for the use of harmonic mean calculations to describe the central tendency of pharmacokinetic parameters of cyclosporin-A under the conditions studied. The value of harmonic mean values for pharmacokinetic parameters in other patient populations or with other assay methods for cyclosporin remain to be studied.

Bias↗
PubMed1989

The impact of body weight on cyclosporine pharmacokinetics in renal transplant recipients.

In order to assess the effect of body weight on cyclosporine disposition, 45 adult uremic candidates for renal transplantation underwent detailed nutritional assessment and pharmacokinetic analysis. There were 10 obese and 35 nonobese patients defined as actual body weight (ABW) greater than 125 Per cent of ideal body weight (IBW), and arm fat area greater than 90th percentile. There was no significant difference in demographic variables such as age, sex, number of diabetics, IBW, serum lipids, or liver function tests between the 2 groups. Although there was a significant difference in ABW, pharmacokinetic analyses failed to demonstrate significant differences in bioavailability, elimination half-life, clearance, or apparent steady state volume of distribution when these calculations were normalized by IBW, body surface area, or as absolute values. Multiple stepwise linear regression failed to demonstrate a significant correlation between serum lipids or body size measurements and these parameters. When dosed according to ABW, obese recipients of renal allografts had a mean serum RIA trough level of 227 ng/ml as compared to 121 ng/ml in nonobese recipients on day 7. Therefore in order to achieve comparable drug concentrations in the early transplant period, CsA should be given to obese patients based on their IBW.

Adult↗
PubMed1987

Influence of cyclosporine on posttransplant blood pressure response.

The suggestion that hypertension is more prevalent in renal allograft recipients receiving cyclosporine (CyA), particularly those displaying nephrotoxicity, was tested by reviewing 200 patients' courses, including 92 cadaver (CAD) and 58 living-related (LRD) transplants using CyA and prednisone immunosuppression, and 19 CAD and 31 LRD transplants using azathioprine (Aza) and prednisone, all of whom had at least 1 year posttransplant complete outpatient follow-up. Both groups had a mean age of 33 years with a similar distribution of renal failure etiologies. Renal function was significantly impaired in the CyA group at all intervals (P less than .001, t test). The prevalence of hypertension was higher in the CyA group at all intervals, becoming significant at 12 (P less than .01) and 24 (P less than .05) months following transplantation (chi 2). While there was only a significant difference in mean diastolic BP at 12 months (P less than .05, t test), the mean number of antihypertensive and/or diuretic medications was significantly greater in the CyA group at 1 and 6 months (P less than .001) and at 12 months (P less than .01). By 24 months, the mean number of all antihypertensive and/or diuretic medications was no longer significantly different. However, the antihypertensive and diuretic requirements of the CyA group diminished with time, suggesting that the hypertension is not progressive if the CyA serum trough levels are maintained in the nontoxic range (less than 200 ng/mL).

Adolescent↗
PubMed1987

Cyclosporine toxicity: the effect of combined therapy using cyclosporine, azathioprine, and prednisone.

Forty-nine patients among 360 who received renal transplants under cyclosporine (CsA)/prednisone (Pred) immunosuppression required alteration of the immunosuppressive regimen because of intractable nephrotoxicity. Twenty-five patients, converted totally to azathioprine (Aza)/Pred, suffered intractable nephrotoxicity with no associated evidence suggesting ongoing rejection. The results with Aza/Pred conversion were disappointing because of an unacceptably high incidence of rejection and allograft loss. Twenty-four patients with intractable CsA nephrotoxicity were, therefore, treated using an alternative approach combining Aza with aggressive CsA dose reduction, and continued Pred therapy. All patients tolerated initiation of Aza without complication; allograft rejection was not common. Renal function improved for 23 of the 24 (96%) CsA/Aza/Pred patients with mean serum creatinine levels falling from 3.5 +/- 0.5 mg/dL to 2.2 +/- 0.4 mg/dL after a mean follow-up of 14 months (P less than .001). Among 18 patients observed at least 12 months, seven (39%) enjoyed serum creatinine values less than or equal to 2 mg/dL. Nine CsA/Aza/Pred-treated patients (37.5%) required hospitalization because of infectious complications, all of which resolved with temporary reduction of immunosuppression and specific antimicrobial therapy when indicated. One patient sustained acute allograft rejection as a result of patient noncompliance, and one patient on a seemingly appropriate CsA/Aza/Pred dose responded initially to steroid pulse antirejection therapy; however, renal function again worsened. Two patients developed progressive renal dysfunction due to chronic rejection, and returned to dialysis 13 and 17 months, respectively, following initiation of CsA/Aza/Pred. Overall, the actuarial graft survival for CsA/Aza/Pred-treated patients was 100% at 1 year, and 84% at 2 years.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1987

Hepatobiliary and pancreatic complications of cyclosporine therapy in 466 renal transplant recipients.

Two hundred twenty-eight patients from a total of 466 (49%) receiving renal allografts under cyclosporine/prednisone (CsA/Pred) immunosuppression experienced at least one episode of posttransplant hepatotoxicity. All patients were documented to have normal serum bilirubin, serum glutamic oxaloacetic transaminase (SGOT), serum glutamic pyruvate transaminase (SGPT), lactic acid dehydrogenase (LDH), and alkaline phosphatase (AP), as well as negative results of biliary ultrasound and upper gastrointestinal contrast examinations prior to transplantation. Hepatotoxic episodes usually were self-limited (82%), and generally occurred during the very early posttransplant period (76%). Liver function abnormalities included hyperbilirubinemia (48% of patients), elevated SGOT (47%), SGPT (73%), LDH (84%), and AP (59%). The CsA serum trough radioimmunoassay (RIA) was relatively high among hepatotoxic patients with a mean value of 225 +/- 17 ng/ml. Pharmacokinetic parameters, including bioavailability and drug clearance, were significantly altered among this group of patients. The management strategy of CsA dose reduction was effective; however, 11 patients (2.4%) developed biliary calculous disease posttransplant while under CsA/Pred immunosuppression. Seven patients had cholelithiasis, and two patients underwent choledochoduodenostomy because of primary choledocholithiasis. The results contrast with 279 renal transplant recipients from an overlapping nonrandomized group treated with azathioprine (Aza)/Pred in whom cholelithiasis was not identified. Pancreatic abnormalities were relatively common, but clinical pancreatic disease occurred in only six patients. There were two episodes of acute pancreatitis, three patients developed pancreatic abscess, and one patient developed a pancreatic pseudocyst. The apparent proclivity of CsA-treated patients to develop biliary calculous disease, and the occurrence of serious pancreatic complications in a small percentage of patients did not affect the majority of CsA-treated patients. They may, however, represent important problems associated with the use of this immunosuppressive agent.

Adult↗
PubMed1987

Multivariate analysis of risk factors impacting on immediate and eventual cadaver allograft survival in cyclosporine-treated recipients.

A multivariate analysis dissected the impact of donor procurement variables, immunologic risk factors, and alternate cyclosporine and prednisone induction immunosuppressive regimens on the early and eventual function of 303 consecutive cadaveric renal allografts. Primarily warm, but to a slight extent cold, ischemia time had an adverse impact on allograft function, as did the requirement for vasopressor or diuretic therapy. The occurrence of initial graft non-function adversely affected the probability of three-month graft survival, but did not alter either the longevity of organs, which subsequently recovered function, or patient mortality rate. The major immunologic risk factor was a second or multiple transplant, which was associated with an increased incidence of early graft failure, and impaired renal function in successful transplants. Correlations with HLA-B and DR matching were reflected in the quality of renal function, but not in graft survival rates. Cyclosporine (CsA) administration by continuous intravenous infusion, in order to avert initial elevated mean three-day, serum radioimmunoassay drug levels reduced the incidence of initial graft non-function. High levels were also associated with impaired early and eventual renal function. Rapid posttransplant taper of corticosteroids to 30 mg prednisone by day six was associated with a greater incidence of rejection episodes and early graft failure than a taper that achieved 30 mg prednisone at 60 days. Both the serum creatinine value and the degree of hypertension observed at one month afforded good prognostic indices of eventual graft survival. Therefore, renal allografts in CsA-treated patients were sensitive not only to adverse donor and immunologic risk factors, but also to excessive CsA drug levels in the early postoperative period. These findings suggest an induction immunosuppressive strategy utilizing slightly higher initial doses of steroids for CsA-sparing during the first three days, followed by increased, but judicious, administration of CsA to achieve steroid-sparing by virtue of effective rejection prophylaxis.

Cyclosporins↗