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J S Najarian

Publications and source records attributed to J S Najarian.

At least 19 recordsLinked to original sources
PubMed2004

Evolution of immunosuppression at the University of Minnesota.

Immunosuppressive protocols at the University of Minnesota have evolved from identical immunosuppression for all recipients (prednisone, azathioprine, and antilymphocyte globulin) to differing protocols for living (triple therapy) and cadaver (sequential therapy) donor recipients, and then to our current protocol in which all recipients receive induction therapy with rapid discontinuation of prednisone. At the same time, progress has been made in the prevention and treatment of cytomegalovirus infection along with numerous parallel improvements in patient care, including in anesthesia, dialysis, and intensive care unit care. The net result has been an incremental improvement in recipient and graft survival.

Animals↗
PubMed2001

Kidney transplantation in young children: should there be a minimum age?

The optimal age for transplantation in children with end-stage renal disease remains controversial. Many centers have adopted a policy of waiting until such children reach a certain minimum age or weight, maintaining them on chronic dialysis until then. Their policy is based on historical data showing inferior graft survival in very young children. We feel that with proper donor selection and recipient care, comparable results can be achieved in very young age groups. We herein present our results with kidney transplantation in children <1 year old. Between 1 January 1984 and 31 December 1999, we performed 321 kidney transplants in children < or =13 years at the University of Minnesota. We analyzed our results in three age groups: <1 year (n=30), 1 through 4 years (n=122), and 5 through 13 years (n=169). We found no significant differences in patient or graft survival rates between the three groups. Almost all our infant (<1 year) recipients underwent primary transplants from living donors (LDs). However, even when we compared results only of primary LD transplants between the three groups, we found no significant differences. To date, all our infant recipients are alive and well, 24 (80%) with a functioning original graft. Causes of the 6 graft losses were chronic rejection (n=3), vascular thrombosis (n=2), and recurrent disease (n=1). Infants had significantly lower incidences of acute and chronic rejection compared with older recipients, but a tendency to higher incidences of delayed graft function and vascular thrombosis. Infants had significant increases in weight post transplant: the mean standard deviation score rose from -2.8 pre transplant to -0.2 by age 5 years and to +1.8 by age 10 years. The improvement in height was less marked: the mean standard deviation rose from -3.2 pre transplant to -1.6 by age 5 years and to -1.4 by age 10 years. Kidney transplant results in very young children can be comparable to those in older children. There need be no minimum age for performing a kidney transplant. The timing of the transplant should not be based on age or size alone.

Acute Disease↗
PubMed2001

Pediatric kidney transplantation: historic hallmarks and a personal perspective.

Over the last five decades, pediatric kidney transplantation (Tx) has proved to be a viable therapeutic alternative for children with end-stage renal disease. Patient and graft survival rates, as well as long-term quality of life, have improved dramatically during this time, as a result of advances in surgical techniques, immunosuppression, and pre- and post-operative care. The inspired, hard work of multi-disciplinary clinical teams, combined with the determination and courage of the young patients and their families, have fueled the success of pediatric kidney Tx. It is with similar optimism and drive that we face the great challenges of the future, such as maximizing the donor pool and inducing tolerance.

Graft Survival↗
PubMed2001

Rapid discontinuation of steroids in living donor kidney transplantation: a pilot study.

UNLABELLED: Steroids are associated with significant postoperative complications (hypertension, cosmetic changes, bone loss, hyperlipidemia, diabetes, and cataracts). Most develop early; in addition, late post-transplant steroid withdrawal in kidney transplant recipients has been associated with increased acute rejection (AR). To obviate these problems, we studied outcome of a protocol of rapid discontinuation of prednisone (RDS) (steroids stopped on POD6). Between November 1, 1999 and October 31, 2000, 51 adult living donor (LD) first transplant recipients (2 HLA-id, 28 non-id relative, 21 LURD) were immunosuppressed with thymoglobulin (1.25 mg/kg intraoperatively and then qdx4); prednisone (P) (500 mg methylprednisolone intraoperatively, 1 mg/kg x 1 day, 0.5 mg/kg x 2 days, 0.25 mg/kg x 2 days, then d/c); MMF, 1 g b.i.d.; and CSA, 4 mg/kg b.i.d. adjusted to achieve levels of 150-200 ng/mL (by HPLC). Exclusion criteria were delayed graft function or primary disease requiring P. Minimum follow-up was 5.5 months (range 5.5 to 17.5 months). Outcome was compared vs. previous cohorts of LD recipients immunosuppressed with P/AZA/CSA (n = 171) or P/MMF/CSA (n = 43) (both without antibody induction). RESULTS: For the RDS group, average CSA level (+/- S.E.) at 3 and 6 months was 190 +/- 12 and 180 +/- 9; avg. MMF dose, 1.7 +/- 0.1 g and 1.7 +/- 0.1 g. There was no significant difference in 6- and 12-month actuarial patient survival, graft survival and rejection-free graft survival between recipients on the RDS protocol vs. historical controls. For RDS recipients, actuarial 6- and 12-month rejection-free graft survival was 87%. Of the 51 RDS recipients, five (10%) have had AR (at 20 days, 1 month, 3 months, 3 months, and 3.5 months post-transplant). After treatment, all five were maintained on 5 mg P; there have been no second AR episodes. Two additional recipients were started on 5 mg P due to low white blood count (WBC) and low/no MMF. Of the 51 grafts, one has failed (death with function). Average serum Cr level (+/- S.E.) at 3 and 6 months for RDS recipients was 1.7 +/- 0.5 (NS vs. historical controls). CONCLUSION: For low-risk LD recipients, a kidney transplant with an RDS protocol does not increase risk of AR or graft loss. Future studies will need to be done to assess AR rates with an RDS protocol in cadaver transplant recipients and in recipients with delayed graft function.

Azathioprine↗
PubMed2001

Lessons learned from more than 1,000 pancreas transplants at a single institution.

OBJECTIVE: To determine outcome in diabetic pancreas transplant recipients according to risk factors and the surgical techniques and immunosuppressive protocols that evolved during a 33-year period at a single institution. SUMMARY BACKGROUND DATA: Insulin-dependent diabetes mellitus is associated with a high incidence of management problems and secondary complications. Clinical pancreas transplantation began at the University of Minnesota in 1966, initially with a high failure rate, but outcome improved in parallel with other organ transplants. The authors retrospectively analyzed the factors associated with the increased success rate of pancreas transplants. METHODS: From December 16, 1966, to March 31, 2000, the authors performed 1,194 pancreas transplants (111 from living donors; 191 retransplants): 498 simultaneous pancreas-kidney (SPK) and 1 simultaneous pancreas-liver transplant; 404 pancreas after kidney (PAK) transplants; and 291 pancreas transplants alone (PTA). The analyses were divided into five eras: era 0, 1966 to 1973 (n = 14), historical; era 1, 1978 to 1986 (n = 148), transition to cyclosporine for immunosuppression, multiple duct management techniques, and only solitary (PAK and PTA) transplants; era 2, 1986 to 1994 (n = 461), all categories (SPK, PAK, and PTA), predominantly bladder drainage for graft duct management, and primarily triple therapy (cyclosporine, azathioprine, and prednisone) for maintenance immunosuppression; era 3, 1994 to 1998 (n = 286), tacrolimus and mycophenolate mofetil used; and era 4, 1998 to 2000 (n = 275), use of daclizumab for induction immunosuppression, primarily enteric drainage for SPK transplants, pretransplant immunosuppression in candidates awaiting PTA. RESULTS: Patient and primary cadaver pancreas graft functional (insulin-independence) survival rates at 1 year by category and era were as follows: SPK, era 2 (n = 214) versus eras 3 and 4 combined (n = 212), 85% and 64% versus 92% and 79%, respectively; PAK, era 1 (n = 36) versus 2 (n = 61) versus 3 (n = 84) versus 4 (n = 92), 86% and 17%, 98% and 59%, 98% and 76%, and 98% and 81%, respectively; in PTA, era 1 (n = 36) versus 2 (n = 72) versus 3 (n = 30) versus 4 (n = 40), 77% and 31%, 99% and 50%, 90% and 67%, and 100% and 88%, respectively. In eras 3 and 4 combined for primary cadaver SPK transplants, pancreas graft survival rates were significantly higher with bladder drainage (n = 136) than enteric drainage (n = 70), 82% versus 74% at 1 year (P =.03). Increasing recipient age had an adverse effect on outcome only in SPK recipients. Vascular disease was common (in eras 3 and 4, 27% of SPK recipients had a pretransplant myocardial infarction and 40% had a coronary artery bypass); those with no vascular disease had significantly higher patient and graft survival rates in the SPK and PAK categories. Living donor segmental pancreas transplants were associated with higher technically successful graft survival rates in each era, predominately solitary (PAK and PTA) in eras 1 and 2 and SPK in eras 3 and 4. Diabetic secondary complications were ameliorated in some recipients, and quality of life studies showed significant gains after the transplant in all recipient categories. CONCLUSIONS: Patient and graft survival rates have significantly improved over time as surgical techniques and immunosuppressive protocols have evolved. Eventually, islet transplants will replace pancreas transplants for suitable candidates, but currently pancreas transplants can be applied and should be an option at all stages of diabetes. Early transplants are preferable for labile diabetes, but even patients with advanced complications can benefit.

Adolescent↗
PubMed2001

2,500 living donor kidney transplants: a single-center experience.

OBJECTIVE: To review a single center's experience and outcome with living donor transplants. SUMMARY BACKGROUND DATA: Outcome after living donor transplants is better than after cadaver donor transplants. Since the inception of the authors' program, they have performed 2,540 living donor transplants. For the most recent cohort of recipients, improvements in patient care and immunosuppressive protocols have improved outcome. In this review, the authors analyzed outcome in relation to protocol. METHODS: The authors studied patient and graft survival by decade. For those transplanted in the 1990s, the impact of immunosuppressive protocol, donor source, diabetes, and preemptive transplantation was analyzed. The incidence of rejection, posttransplant steroid-related complications, and return to work was determined. Finally, multivariate analysis was used to study risk factors for worse 1-year graft survival and, for those with graft function at 1 year, to study risk factors for worse long-term survival. RESULTS: For each decade since 1960, outcome has improved after living donor transplants. Compared with patients transplanted in the 1960s, those transplanted in the 1990s have better 8-year actuarial patient and graft survival rates. Death with function and chronic rejection have continued to be a major cause of graft loss, whereas acute rejection has become a rare cause of graft loss. Cardiovascular deaths have become a more predominant cause of patient death; infection has decreased. Donor source (e.g., ideally HLA-identical sibling) continues to be important. For living donor transplants, rejection and graft survival rates are related to donor source. The authors show that patients who had preemptive transplants or less than 1 year of dialysis have better 5-year graft survival and more frequently return to full-time employment. Readmission and complications remain problems; of patients transplanted in the 1990s, only 36% never required readmission. Similarly, steroid-related complications remain common. The authors' multivariate analysis shows that the major risk factor for worse 1-year graft survival was delayed graft function. For recipients with 1-year graft survival, risk factors for worse long-term outcome were pretransplant smoking, pretransplant peripheral vascular disease, pretransplant dialysis for more than 1 year, one or more acute rejection episodes, and donor age older than 55. CONCLUSIONS: These data show that the outcome of living donor transplants has continued to improve. However, for living donors, donor source affects outcome. The authors also identify other major risk factors affecting both short- and long-term outcome.

Adolescent↗
PubMed2000

Immunologic and nonimmunologic factors: different risks for cadaver and living donor transplantation.

BACKGROUND: There is a debate about the relative contribution of immunologic (rejection) and nonimmunologic (limited nephron mass) factors in long-term graft survival. METHODS: Using multivariate analysis, we studied the association of the following variables with outcome: delayed graft function (DGF), acute rejection, recipient race (black vs. nonblack), donor age (<50 vs. > or =50), donor race, and donor and recipient gender. Because of the association between DGF and rejection, recipients were grouped as follows: DGF, rejection; DGF, no rejection; no DGF, rejection; no DGF, no rejection. Data were analyzed on 1199 first kidney transplants in adults (752 living donor, 447 cadaver donor) done between January 1, 1985 and December 31, 1996. Two analyses were done: first, all transplants; second, only those with > or =1 year survival. For both, there was no difference in risk factors if death with function was or was not censored. RESULTS: For all cadaver transplant recipients, risk factors were acute rejection, DGF plus rejection, black recipient race, and donor age > or =50. For living donor recipients, only acute rejection was a risk factor. When only 1-year graft survivors were considered, risk factors were the same: for cadaver recipients, risk factors were acute rejection, DGF plus rejection, black recipient race, and donor age > or =50; for living donor recipients the risk factor was rejection. CONCLUSION: We found immunologic factors (rejection with or without DGF) to be significant in both living donor and cadaver donor transplants. Nonim. munologic factors (donor age, recipient race) were significant only in cadaver donor transplants.

Acute Disease↗
PubMed2000

Should I accept this kidney?

BACKGROUND: Transplant candidates frequently ask whether they should, based on information available at the time, accept a cadaver kidney or wait for a potentially better one. METHODS: We analyzed 937 first and second cadaver transplants done between January 1, 1984 and December 31, 1997 to determine if information available at the time an offer is made could be used to predict long-term graft survival. RESULTS: By Cox regression, risk factors for worse long-term graft survival were older donor age, cardiovascular or cerebrovascular cause of donor death, and delayed graft function (DGF). HLA-ABDR mismatch was marginally significant. Whether DGF will occur is not known at the time of an offer, but risk factors can be determined; we found these to be older donor age and > 10% panel-reactive antibodies (PRA) at transplantation (by Cox regression). Using these variables (PRA, ABDR mismatch, donor age, and donor cause of death) known at the time of an offer, we calculated the relative risk of worse long-term graft survival for each subgroup (Table 3 in manuscript). In general, older age and donor death from cardiovascular or cerebrovascular disease were associated with worse outcome. Kidneys from donors of < 50 yr had the best outcome, irrespective of match. CONCLUSION: The data provided can be used to help guide patients as to whether they are better off accepting an offered kidney or waiting for a potentially better one. If an offer is declined, the next kidney may have a potentially worse outcome.

Adolescent↗
PubMed2000

5,000 kidney transplants--a single-center experience.

Between 6/1963 and 12/1998, 5,069 kidney transplants were done at the University of Minnesota. Of these, about half have been living donor, half cadaver. The majority (83%) have been primary transplants. Recipients were grouped in 6 eras based on changes in our immunosuppressive protocols--6/63-12/67 (n = 98); 1/68-7/79 (n = 1,188); 8/79-6/84 (n = 789); 7/84-9/90 (n = 1,006); 10/90-12/95 (n = 1,050; 1/96-12/98 (n = 718)--and their outcomes were compared. Recent eras contained a higher proportion of recipients aged > 50. Since the inception of the program, there has been a steady improvement in actuarial patient survival, graft survival, and death-censored graft survival. Short-term outcome for primary and retransplant recipients has been similar; however, long-term outcome seems worse for retransplant recipients. Importantly, acute rejection and infectious death have become rare causes of graft loss. Chronic rejection and death with function (most often due to a cardiovascular event) have become the predominant causes of graft loss. Recent changes in immunosuppressive protocols (Era VI) have included more aggressive attempts to maintain CsA levels > 150 ng/ml (by HPLC) in the first 3 months and the substitution of mycophenolate mofetil for azathioprine. As a result, the incidence of acute and chronic rejection has decreased and graft survival has improved.

Adolescent↗
PubMed1999

Decreased acute rejection in kidney transplant recipients is associated with decreased chronic rejection.

OBJECTIVE: To determine whether a recent decrease in the rate of acute rejection after kidney transplantation was associated with a decrease in the rate of chronic rejection. SUMMARY BACKGROUND DATA: Single-institution and multicenter retrospective analyses have identified acute rejection episodes as the major risk factor for chronic rejection after kidney transplantation. However, to date, no study has shown that a decrease in the rate of acute rejection leads to a decrease in the rate of chronic rejection. METHODS: The authors studied patient populations who underwent transplants at a single center during two eras (1984-1987 and 1991-1994) to determine the rate of biopsy-proven acute rejection, the rate of biopsy-proven chronic rejection, and the graft half-life. RESULTS: Recipients who underwent transplantation in era 2 had a decreased rate of biopsy-proven acute rejection compared with era 1 (p < 0.05). This decrease was associated with a decreased rate of biopsy-proven chronic rejection for both cadaver (p = 0.0001) and living donor (p = 0.08) recipients. A trend was observed toward increased graft half-life in era 2 (p = NS). CONCLUSIONS: Development of immunosuppressive protocols that decrease the rate of acute rejection should lower the rate of chronic rejection and improve long-term graft survival.

Acute Disease↗
PubMed1998

Venous thromboembolic complications after kidney and kidney-pancreas transplantation: a multivariate analysis.

BACKGROUND: We reviewed the incidence of and risk factors for venous thromboembolic complications in our population of kidney (KTx) and simultaneous kidney-pancreas transplant (SPK) recipients. METHODS: Information was collected retrospectively from a database on 1833 KTx and 276 SPK recipients who underwent transplant surgery between January 1985 and August 1995. RESULTS: The incidence of deep venous thrombosis (DVT) was 6.2% (n= 132), with significantly higher rates after SPK (18.1%) vs. KTx (4.5%) (P < 0.001). The number of DVT episodes was highest in the first month; 17.5% occurred during this time. For KTx recipients, early thrombotic events were more common on the side of the graft (P=0.03); however, after 1 month, no correlation existed between the side of the graft and the side of DVT. For SPK recipients, DVT tended to be more common on the side of the pancreas (57%) vs. the kidney (43%) (P=0.10). By multivariate analysis, risk factors for DVT were: age > 40 years (odds ratio [OR]=2.2, P < 0.001), diabetes mellitus (DM) (OR=2.0, P=0.002), previous DVT (OR=4.4, P=0.001), and SPK transplant (OR=2.8, P < 0.001). Pulmonary embolus (PE) was identified in 44 recipients (incidence, 2.1%) and was fatal in 13 (30%). The incidence was significantly higher in SPK (4.71%) vs. KTx recipients (1.69%) (P < 0.01). The risk of death from PE was 0.5% in KTx recipients and 1.37% in SPK recipients (P=0.08). Risk factors for PE included DM (OR=2.6, P=0.005) and recent DVT (OR=8.9, P=0.0001). CONCLUSIONS: Based on risk and extrapolating from the general surgical literature, our recommendations for prophylaxis against DVT are use of graduated compression stockings for all recipients and, in addition, low-dose heparin for moderate and high-risk recipients (previous DVT, SPK, age > 40 years, DM).

Adult↗
PubMed1998

Kidney transplantation in children younger than 1 year using cyclosporine immunosuppression.

OBJECTIVE: The optimal age for transplantation in children with end-stage renal disease remains controversial. Supported by national data, many centers recommend dialysis until the child reaches a certain minimum age. The authors' policy, however, has been to encourage living donor (LD) transplants for young children, with no minimum age restriction. METHODS: Between January 1, 1984, and December 31, 1996, the authors performed 248 kidney transplants in children younger than age 13 years, using cyclosporine as the primary immunosuppressive agent. Recipients were analyzed in three age groups: group 1, younger than age 1 year (n = 26); group 2, age 1 through 4 (n = 92); and group 3, age 5 through 13 (n = 130). Almost all recipients in group 1 underwent a primary LD transplant. Therefore, to compare results more meaningfully among the three age groups, only primary LD transplants were analyzed (group 1, n = 25; group 2, n = 59; group 3, n = 58). RESULTS: In primary LD transplants, no significant difference was noted among the age groups in 1-and 5-year patient or graft survival rates. To date, all 25 recipients from group 1 are alive and well; 19 still have a functional original graft. Causes of graft loss in the remaining six recipients were chronic rejection (n = 3), vascular thrombosis (n = 2), and recurrent disease (n = 1). The incidence of acute rejection in group 1 recipients was lower than in the two older groups. However, the incidence of delayed graft function was slightly higher in the youngest group than in the two older groups. For recipients in group 1, growth (as measured by weight) improved significantly posttransplant: the mean standard deviation score rose from -2.8 pretransplant to -0.2 by age 5 and to +1.8 by age 10. The improvement in height was not as dramatic: the mean standard deviation score rose from -3.2 pretransplant to -1.6 by age 5 and to -1.4 by age 10. CONCLUSIONS: Kidney transplantation in young children, including those younger than 1 year old, can achieve results comparable to those in older children. As long as an adult LD is available, the timing of the transplant should be based on renal function rather than age.

Adolescent↗
PubMed1998

The acutely ischemic extremity after kidney transplant: an approach to management.

BACKGROUND: The purpose of this study was to review arterial thromboembolic complications presenting with an acutely ischemic lower extremity after a kidney (KTx) or simultaneous kidney-pancreas transplantation (SPK) and to describe an approach to their management. METHODS: We retrospectively reviewed all such transplantations (a total of 2109) performed between January 1985 and August 1995. We identified 16 recipients (incidence, 0.76%) in whom an acutely ischemic leg developed during the immediate postoperative period (within the first 48 hours). RESULTS: Of the 16 recipients, eight underwent a KTx (incidence, 0.45%) and eight underwent an SPK transplantation (incidence, 2.90%). Median age was 38 years (range, 15 months to 61 years). Thirteen had insulin-dependent diabetes mellitus (IDDM), a significantly higher incidence than in the control group (i.e., transplant recipients without this complication) (p < 0.01). Peripheral vascular disease (PVD) was documented before operation in eight (50%) of the recipients (vs 8.9% in the control group) (p < 0.01). Ten were uremic (on chronic dialysis) before transplantation; six were nonuremic (not on dialysis). Intraoperatively, 14 had moderate to severe atherosclerotic disease affecting the iliac vessels, seven of whom required some manipulation of the artery (either endarterectomy or tacking of the intima) to make it suitable for anastomosis. Heparin was administered systemically during cross clamping to only four. Most of the 16 recipients showed symptoms or signs of arterial occlusion within the first few hours after operation. The most common symptom was pain; the most common physical finding was loss of femoral and distal pulses. Thirteen recipients had moderate to severe ischemia, as judged by physical examination; 15 returned to the operating room for surgical exploration. Eight underwent thrombectomy through an inguinal incision, with successful restoration of flow. Seven underwent exploration through the initial incision because of concern regarding the viability of the transplanted organ; five of them required transplant nephrectomy because of simultaneous thrombosis of the renal artery. No patient needed a bypass procedure to restore flow. Long-term morbidity as a result of the arterial occlusion was related to the severity and length of ischemia. CONCLUSIONS: On the basis of these results, we suggest the following recommendations: (1) all patients should undergo a thorough peripheral vascular examination before and after transplantation; (2) patients at higher risk for arterial thromboembolic complications (e.g., those with significantly diseased vessel at intraoperative examination, nonuremic patients) should receive intraoperative systemic heparin before cross clamping of the artery; and (3) patients with signs or symptoms suggesting arterial occlusion after operation should undergo prompt surgical exploration.

Acute Disease↗