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Biomedical subjects

A J Matas

Publications and source records attributed to A J Matas.

At least 145 records · Page 8Linked to original sources
PubMed1994

Successful long-term outcome with 0-haplotype-matched living-related kidney donors.

The waiting list for cadaver kidney transplantation continues to grow. Yet there has been little increase in the number of living-donor transplants. At many centers, willing relatives are turned down as potential donors because of poor HLA ABDR matching with the recipient. It has been our policy to accept the 0-haplotype-match (0-HTM) living-related donor. We studied long-term (6-year) outcome of 0-HTM transplants compared with the outcome of transplants from 1- and 2-HTM recipients and from cadaver donors. Since 1984, 352 adults have received primary living-related renal transplants, and had a minimum of 1 year of follow-up: 92 2-HTM, 216 1-HTM, and 44 0-HTM. In the same period and with the same follow-up, 362 adults have received primary cadaver (CAD) renal transplants. Immunosuppression consisted of cyclosporine, azathioprine, and prednisone (triple therapy) for living-donor and sequential therapy for CAD recipients. ABDR match (mean +/- SD) for 0 HTM was 1.3 +/- 8; CAD, 2.0 +/- 1.6; % peak panel-reactive antibodies (PRA) for 0 HTM was 1.2 +/- 5.3; 1 HTM, 6.7 +/- 20; 2 HTM, 7.5 +/- 21; CAD, 15.5 +/- 30. The percentage of PRA at the time of transplant for 0 HTM was .7 +/- 4.4; 1 HTM, 4.1 +/- 1.6; 2 HTM, 6 +/- 18; CAD, 7.2 +/- 20. While the number of ABDR matches was significantly fewer for 0 HTM than for the other groups, the % PRA at transplant and the peak % PRA were less in the 0-HTM group. Other demographics were not significantly different. Patient survival was significantly lower in the CAD group vs. 2-HTM recipients (P < .05). The living-related grafts had significantly greater survival than the CAD grafts (P < .05), but there was no significant difference between 0-, 1-, and 2-HTM graft survival. The most common causes of graft loss in all groups were death and chronic rejection. In our experience, the long-term graft survivals of 0-HTM and 1-HTM transplants are the same, and both are superior to CAD results, using 0-HTM living-related donor transplants should be continued and encouraged.

Adult↗
PubMed1994

Pharmacokinetics of FK506 after intravenous and oral administration in patients awaiting renal transplantation.

The authors examined the safety and pharmacokinetics of FK506, a new hepatically metabolized immunosuppressant, after single-dose intravenous (i.v.) infusion (20 micrograms.kg(-1) x 4 hours-1) and oral (80 micrograms/kg) administration in six nondialysis patients, aged 27 to 53 years, with chronic renal failure awaiting transplantation. A two-period, randomized, crossover study protocol was used with blood samples drawn for 72 hours after each dose and a washout period of 4 days. Whole-blood FK506 levels were determined using a standard, two-step, nonspecific enzyme immunoassay. There were no significant changes in vital signs, EKG, or complete laboratory test battery for any patient during the entire study period. No side effects were noted after i.v. or oral FK506 dosing. Mean +/- SD distribution half life was 0.9 +/- 0.2 hours, elimination half life (t1/2 beta) 33 +/- 8 hours, total body clearance (CL) 2.4 +/- 1.1 L/hour, and bioavailability 14 +/- 12%. There was no significant correlation between serum creatinine (Cr) and CL (r = 0.36) or between Cr and t1/2 beta (r = -0.30). It was found that FK506 is incompletely and erratically absorbed after oral administration and is rapidly distributed outside the blood compartment after IV dosing. An extended sampling period seems necessary to accurately characterize the slow elimination phase of FK506.

Administration, Oral↗
PubMed1994

Causes of kidney allograft loss in a large pediatric population at a single center.

At our institution, 521 kidney transplants were performed in 429 children (mean age 8.7 +/- 5.6-years) between 1969 and 1991. Of these transplants, 408 were primary, 113 were retransplants, 347 were living related, 171 were cadaver, and 3 were living nonrelated. Immunosuppression consisted of prednisone, azathioprine, and Minnesota antilymphocyte globulin (non-CSA) in 339 patients, total lymphoid irradiation in 8, and, more recently, cyclosporine (CSA) in addition in 168 patients. Average follow-up was 8.8 +/- 6.0 years. Actuarial graft survival in the non-CSA versus CSA groups at 1 year was 77.0% versus 85.7%; at 5 years, 59.6% versus 71.9%. Of 136 non-CSA patients, causes of graft loss at 5 years included: chronic rejection in 55 (40.4%), acute rejection in 27 (19.9%), recurrent disease in 16 (11.8%), technical complications in 8 (5.9%), infectious complications in 4 (2.9%), other causes in 5 (3.7%), and death with a functioning graft in 21 (15.4%). Of 40 CSA patients, causes of graft loss at 5 years included: chronic rejection in 16 (40.0%), acute rejection in 8 (20.0%), recurrent disease in 6 (15.0%), technical complications in 3 (7.5%), other causes in 2 (5.0%), and death with a functioning graft in 5 (12.5%). The causes of graft loss did not significantly differ in the non-CSA and CSA groups. Chronic rejection was the most common cause of graft loss in both groups. Research focusing on chronic rejection is needed to improve graft outcome in pediatric kidney transplantation.

Academic Medical Centers↗
PubMed1994

Cellular rejection in discordant xenografts when hyperacute rejection is prevented: analysis using adoptive and passive transfer.

Hyperacute rejection of discordant xenografts occurs rapidly, precluding cellular infiltration. Thus the role of cellular rejection in discordant xenografts is debated. Using adoptive transfer of sensitized splenocytes and passive transfer of sensitized serum, we evaluated the influence of cellular and humoral elements on cellular infiltration and rejection in the guinea-pig-to-rat discordant xenograft model. Guinea-pig hearts were transplanted into Lewis rats. Pretransplant, rats underwent splenectomy and plasma exchange and were started on daily cobra venom factor injections. Xenografts rejected faster after adoptive (1, 2, 2 and 2 days) or passive (1, 1, 2 and 2 days) transfer than controls (4, 4, 4 and 4 days; p < 0.05). Macrophages and neutrophils were predominant in early prerejection specimens. Over time, cellular infiltrates were dominated by mononuclear cells. Natural killer cells were present in all groups, as were interleukin 2 receptor positive cells. Our data suggest that either sensitized serum or sensitized cells are capable of initiating an accelerated rejection characterized by cellular infiltration. Despite subtle differences, the population of infiltrating cells was similar in each group. Thus, although rejection may be initiated by either cellular or humoral influences, the ultimate result is the same. We have, therefore, established a small animal model to study cellular rejection in discordant xenografts. This model will help evaluate the role of cell subsets and xenoantibodies in xenograft rejection and will help determine the precise relationship between the two when hyperacute rejection is prevented.

Acute Disease↗
PubMed1994

Recurrence of steroid-resistant nephrotic syndrome in kidney transplants is associated with increased acute renal failure and acute rejection.

We performed 73 kidney transplants in 51 patients with steroid-resistant nephrotic syndrome (SRNS) with focal segmental glomerular sclerosis (FSG) ages 18.4 +/- 12.8 (mean +/- SD) years. Recurrence of SRNS, defined by rapid onset of proteinuria, hypoalbuminemia and/or > 95% epithelial cell foot process effacement with or without the presence of FSG, occurred in 26 grafts in 16 patients. Acute renal failure (ARF) occurred in 16 of 26 (61.5%) grafts with recurrence versus 7 of 47 (14.9%) grafts without recurrence (P < 0.0001). ARF occurred in 4 of 9 (44.4%) living-related donor (LRD) recipients with recurrence and 3 of 21 (12.5%) LRD recipients without recurrence (NS). ARF in cadaver donor (CAD) recipients with recurrence was 12 of 17 (70.5%) versus 4 of 23 (17.4%) without recurrence (P < 0.0001). ARF was also higher in LRD or CAD with recurrence than in a control group of non-SRNS patients matched for age, sex and time of transplantation. Graft survival at one year was lower in patients with recurrence and ARF [4 of 16 (25%)] compared to patients with recurrence and no ARF [9 of 11 (82%), P < 0.01]. There was no difference in graft survival in patients without recurrence who did or did not have ARF. One or more acute rejection episodes occurred in all 16 patients with ARF and recurrence, in all 7 patients with ARF without recurrence, and in 7 of 10 patients with recurrence without ARF compared with only 11 of 40 (28%) of patients with neither recurrence nor ARF (P < 0.0001, < 0.001 and < 0.04, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Kidney Injury↗
PubMed1994

Renal transplantation for patients 60 years of older. A single-institution experience.

OBJECTIVE: The authors reviewed renal transplant outcomes in recipients 60 years of age or older. BACKGROUND: Before cyclosporine, patients older than 45 years of age were considered to be at high risk for transplantation. With cyclosporine, the age limits for transplantation have expanded. METHODS: The authors compared patient and graft survival, hospital stay, the incidence of rejection and rehospitalization, and the cause of graft loss for primary kidney recipients 60 years of age or older versus those 18 to 59 years of age. For those patients > or = 60 years transplanted since 1985, the authors analyzed pretransplant extrarenal disease and its impact on post-transplant outcome. In addition, all surviving recipients > or = 60 years completed a medical outcome survey (SF-36). RESULTS: Patient and graft survival for those > or = 60 years of age versus those 18 to 59 years of age were similar 3 years after transplant. Subsequently, mortality increased for the older recipients. Death-censored graft survival was identical in the two groups. There were no differences in the cause of graft loss. Those 60 years of age or older had a longer initial hospitalization, but had fewer rejection episodes and fewer rehospitalizations. Quality of life for recipients 60 years of age or older was similar to the age-matched U.S. population. CONCLUSION: Renal transplantation is successful for recipients 60 years of age or older. Most of them had extrarenal disease at the time of transplantation; however, extrarenal disease was not an important predictor of outcome and should not be used as an exclusion criterion. Post-transplant quality of life is excellent.

Adult↗
PubMed1994

Chronic rejection.

Current immunosuppressive protocols have significantly decreased graft loss to acute rejection but have had no effect on graft loss to chronic rejection. Recently, attention has been focused on the prevention and management of chronic rejection. Centers must come to a uniform definition of this phenomenon so that studies can be compared. It is believed that the definition should include both a typical clinical course and a definitive biopsy. For kidney transplant recipients, the major risk factor for the development of chronic rejection appears to be a previous acute rejection episode. Other important risk factors include low-dose maintenance immunosuppression and previous infection. Noncompliance probably plays a role in some patients. For extrarenal transplant recipients, chronic rejection has been associated with cytomegalovirus infection and/or HLA-DR matching. Immunoregulatory processes posttransplant may modify or attenuate the development of chronic rejection. Large, prospective clinical studies are required to further elucidate risk factors and to determine the effect of intervention.

Chronic Disease↗
PubMed1994

How to identify the best candidates for kidney transplantation: protocols for making the best use of scarce donor organs.

Potential kidney transplant recipients must be thoroughly evaluated to ensure that scarce donor organs are used appropriately. Begin by determining the cause of renal failure (some diseases can recur in transplanted organs; others are associated with increased post-transplant morbidity and mortality). Cancer, active infection, some forms of thrombosis and atherosclerosis, and patient noncompliance usually contraindicate kidney transplantation. A careful patient assessment can identify other factors that may increase the risks of significant postoperative complications; however, most of these factors can be modified before proceeding with transplantation.

Adult↗
PubMed1994

Pediatric renal transplantation at the University of Minnesota: the cyclosporine years.

Overall mortality was low (3.5%) in 199 children who received 217 transplants and quadruple immunosuppression. Graft survival was better in patients on quadruple immunosuppression, compared with historical patients on standard immunosuppression. When censored for deaths with a functioning graft, cumulative graft survival beyond one year was significantly better in patients on quadruple immunosuppression. Acute rejection was more common in CAD recipients and in retransplant recipients. Acute rejection was also more common in patients with FSGS, compared with other causes of ESRD. Preemptive transplants were not associated with a higher incidence of acute rejection. Late acute rejection episodes tended to be associated with a CsA dose < 5 mg/kg/day at one-year posttransplant. Chronic rejection was the major cause of graft loss. Risk factors for graft loss within the first posttransplant year were acute tubular necrosis and an initial CsA dose of < 5 mg/kg/day. Risk factors for graft loss after the first posttransplant year were late onset of the first acute rejection episode and a panel reactivity of > 25% at the time of transplant.

Actuarial Analysis↗
PubMed1994

Complications of ureterovesical anastomosis in kidney transplant patients: the Minnesota experience.

We reviewed urologic complications of 1183 consecutive primary or secondary renal transplants performed with bladder anastomoses at the University of Minnesota Hospital between 1985 and 1993. The Politano-Leadbetter (PL) technique of ureteroneocystostomy was used in 410 patients; the multistich (MS) extravesical technique modified from the methods of Witzel, Sampson, and Lich in 295; and the extravesical single-stitch (SS) technique in 478. Urologic complications occurred in 81 patients (6.8%). Of these complications, 68 (5.7%) were early (< 4 months) and 13 (1.1%) late; 32 (7.8%) were after PL, 17 (5.8%) after MS, and 32 (6.7%) after SS. A total of 13 patients had an anastomotic leak, 7 (1.7%) after PL, 4 (1.4%) after MS, and 2 (0.0004%) after SS; 49 patients had a ureterovesical obstruction, 16 (4.0%) after PL, 12 (4.0%) after MS, and 21 (4.2%) after SS; 5 patients had a ureteropelvic obstruction, 2 (0.5%) after PL, 2 (0.7%) after MS, and 1 (0.2%) after SS; and 14 patients had hematuria, 7 (1.7%) after PL, 1 (0.34%) after MS, and 6 (1.3%) after SS. Of the 81 patients with urologic complications, one (1%) resolved spontaneously; 30 (37%) were treated with temporary percutaneous nephrostomy, 17 (21%) with dilatation and stent; the 14 (17.3%) with hematuria were treated via cystoscopy; 19 (23%) required reoperation. Only 2 (2.5%) patients lost their graft. For both cadaver and living donor recipients, there was no difference between techniques for early and late complications of leakage, stricture, and hematuria. Each technique has certain advantages and each should be in every surgeon's repertoire.

Anastomosis, Surgical↗
PubMed1994

De novo cancer in cyclosporine-treated and non-cyclosporine-treated adult primary renal allograft recipients.

We compared the incidence of de novo tumors developing in 1165 primary adult renal allograft recipients treated with azathioprine (AZA)-prednisone (Pred)-antilymphocyte globulin (ALG) (CONV group) with that in 722 patients receiving cyclosporine (CSA) as part of double (CSA-Pred), triple (CSA-Pred-AZA), or quadruple-therapy (CSA-Pred-AZA-ALG) protocols. Mean +/- SD follow-up was 9.5 +/- 6.4 years for the CONV group and 6.2 +/- 2.7 years for the CSA group. Overall, 124 patients (10.6%) in the CONV group and 34 patients (4.7%) in the CSA group developed malignancies, with nonmelanoma skin cancers and lymphomas comprising 55% and 13% of cancers in the CONV group and 65% and 3% of cancers in the CSA group, respectively. There were no significant differences in overall cancer (p = 0.41) or skin cancer (p = 0.97) incidence between non-CSA-treated and CSA-treated patients by Kaplan-Meier life-table analysis; however, CONV-treated patients demonstrated a higher incidence of lymphoma (p = 0.05). The mean (+/- SD) time to overall and skin cancer occurrence was significantly shorter in the CSA group: 37 +/- 22 versus 90 +/- 52 months (p < 0.001) and 40 +/- 24 versus 92 +/- 52 months, respectively. When the Cox Proportional Hazard Model was utilized to assess the relative importance of age, diabetic status, donor source, sex, and immunosuppressive regimen in determining cancer development, age > or = 50 years and nondiabetic status were significant independent prognostic indicators, while immunosuppressive regimen was not. Graft and patient survival were significantly greater in CONV-treated patients developing cancer than in those who did not.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Kidney transplant outcome with and without right renal vein extension.

Use of the vena cava to extend the right renal vein for cadaver transplantation is controversial. Right renal vein extension permits an easier anastomosis and possibly better positioning of the kidney, but may create a low flow or turbulent state. We studied whether use of a vein extension had an impact on outcome. Between January 1986 and April 1993, 305 cadaver transplant recipients received a right kidney. Of these, 76 received a graft with vein extension. None of the 76 experienced technical vascular complications versus 5 of the 229 (2.2%) without vein extension. There was no difference in 1- and 2-year graft survival for those with versus without extension. We conclude that there is no increased risk with use of the vena cava extension and recommend that the donor team routinely provide the right kidney with the vena cava attached. This allows the recipient team to determine whether an extension is appropriate for the particular recipient.

Anastomosis, Surgical↗