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M R First

Publications and source records attributed to M R First.

At least 55 records · Page 3Linked to original sources
PubMed1998

Characteristics of long-term renal transplant survivors.

Despite the high rates of rejection, allograft failure, and patient death in the early years of renal transplantation, some patients have done remarkably well. Forty-three (17 living related donor and 26 cadaver donor recipients) such patients with an allograft that functioned for 19 years or more (range, 19 to 29 years) were followed up at this center. The patients included 24 men and 19 women, with a mean age at transplantation of 29 years, of whom 39 were white and four were black. At most recent follow-up, the mean daily dose of azathioprine was 104 mg (range, 50 to 175 mg) and that of prednisone was 10 mg (range, 5 to 20 mg). Mean serum creatinine level was 1.6 mg/dL (range, 0.7 to 5.4 mg/dL). Acute rejection occurred in 14 (33%) patients. Nine patients had one episode and five patients had two episodes of acute rejection. Long-term risks to the recipients appeared in the form of coronary artery disease in 10 (23%) patients; malignancy in 13 (30%) patients, which included nine patients with skin malignancy; and chronic hepatitis C virus (HCV) infection in four patients, two of whom died of complications of liver failure. Other complications included avascular bone necrosis in five patients, which required total hip replacement in two patients; hyperlipidemia requiring treatment in 16 (37%) patients; posttransplantation diabetes mellitus in 10 (23%) patients after a median of 17.5 years (range, 1 to 23 years); and hypertension in 23 (53%) patients. There were seven deaths (three of coronary artery disease, two of liver failure, one each of sepsis and malignancy) and eight graft losses (five to death with function, two to chronic rejection, and one to focal and segmental glomerulosclerosis). Although long-term allograft success results in patients receiving minimal amounts of immunosuppression and having good renal function, long-term renal transplant survivors are at risk for significant morbidity even in the third decade posttransplantation.

Adolescent↗
PubMed1998

Use of tacrolimus eliminates acute rejection as a major complication following simultaneous kidney and pancreas transplantation.

This retrospective study illustrates the efficacy of tracrolimus-based immunosuppression following simultaneous kidney and pancreas transplantation. Between March 1995 and December 1996, 24 simultaneous kidney and pancreas transplant recipients received tacrolimus-based maintenance immunosuppression. All patients received sequential therapy with an antilymphocyte agent, azathioprine, prednisone and tacrolimus. The dose of tacrolimus was adjusted to achieve a whole blood trough level of 8-15 ng/mL (IMx). The mean follow-up was 25 months with a median of 26 months (range 12-33 months). A rise in serum creatinine of > 20% over baseline was investigated with a renal biopsy, after mechanical causes for renal dysfunction had been excluded. Mean serum creatinine concentrations at 3, 6, 12, 18 and 24 months post-transplantation were 1.1, 1.2, 1.3, 1.3 and 1.3 mg/dL respectively. The blood glucose concentrations at the corresponding time period were 115, 94, 95, 93 and 95 mg/dL. Four pancreas allografts were lost (three in the immediate post-transplant period due to thrombosis, and one following iliac artery repair for aneurysm). Transient hyperglycemia requiring treatment was seen in 3 patients. There were four (17%) acute rejection episodes--one of the pancreas allograft alone and three involving the kidney. At a mean follow-up of 25 months, the patient survival and renal allograft survival were 100%, with pancreas allograft survival rate of 78.4% (Kaplan-Meier analysis). Nine (37.5%) patients had evidence of tacrolimus toxicity on renal histology. In conclusion, tacrolimus-based maintenance immunosuppression is associated with stable renal and pancreas allograft function, with freedom from acute rejection in 83% of patients.

Adult↗
PubMed1998

Development of Sang-35: a cyclosporine formulation bioequivalent to Neoral.

During a research program, SangStat Medical Corporation developed more than 270 oral cyclosporine formulations. On the basis of animal and clinical trials, Sang-35 was chosen for clinical development, and bioequivalence with the cyclosporine microemulsion Neoral was established. In a cross-over study involving 36 healthy male volunteers, single 500 mg cyclosporine doses of Sang-35 (AUC0-infinity: 13,900 +/- 2470 micrograms.h.L-1, mean +/- standard deviation (SD)) and of Neoral (AUC0-infinity: 14,000 +/- 2900 micrograms.h.L-1) resulted in equal areas-under-the-time-concentration curve (AUC0-infinity). Sang-35 and Neoral were also bioequivalent in healthy male subjects after high-fat meals as well as in female and African-American subjects. In stable kidney transplant patients (n = 12) receiving a mean (+/- SD) cyclosporine dose of mg/d (3.6 +/- 1.6 mg/kg/d), AUC0-12 h after Sang-35 was, as expected, significantly higher than that after Sandimmune (4550 +/- 1858 vs 3468 +/- 1402 micrograms.h.L-1, p < 0.01). Sang-35 and Neoral resulted in equivalent cyclosporine AUC0-12 h values (4120 +/- 1508 and 4377 +/- 1579 micrograms.h.L-1, respectively) in stable kidney transplant patients (dose: 293 +/- 114 mg/d or 3.7 +/- 1.5 mg/kg/d, n = 32). In an additional study, 42 stable kidney graft patients were switched from Sandimmune to Sang-35. Based on a conversion strategy targeting AUC equivalence, only one dose adjustment was required in 55% of the patients, and 95% of patients (40 of 42) needed three or fewer dose adjustments. The mean Sang-35 dose was 7% lower than the mean Sandimmune dose. During the studies, Sang-35 and Neoral exhibited similar safety and tolerability profiles. It is concluded that Sang-35 and Neoral are bioequivalent and that patients can safely and easily be switched from Neoral or, in combination with dose adjustment, from Sandimmune to Sang-35.

Administration, Oral↗
PubMed1997

Efficacy of OKT3 as primary therapy for histologically confirmed acute renal allograft rejection.

BACKGROUND: OKT3 is often used as primary treatment for acute renal allograft rejection. In a retrospective study, we sought to determine the efficacy of OKT3 as a first-line agent in reversing histologically confirmed acute renal allograft rejection. METHODS: Patients with mild to moderate, moderate, or severe acute cellular and acute vascular rejection who had not received any other anti-rejection treatment were included in this analysis. A total of 88 patients, who received OKT3 between 1987 and 1995, fulfilled these criteria. RESULT: Seventy of these patients were renal transplant recipients, and 18 were combined kidney and pancreas transplant recipients. The median time to the diagnosis of rejection from transplantation was 32 days (range, 6 days to 13 years). On histology, 6 were graded as mild to moderate, 36 as moderate, 29 as moderate to severe, and 17 as severe rejection. The mean baseline serum creatinine was 1.62 mg/dl (range, 0.7-10.1 mg/dl), and the mean serum creatinine at the time of diagnosis of rejection was 2.60 mg/dl (range, 1.4-12.7 mg/dl) (P=<0.0001). The mean duration of OKT3 treatment was 11.2 days (range, 8-18 days). The mean serum creatinine at the end of OKT3 treatment was 1.73 mg/dl (range, 0.6-5.0 mg/dl; P=0.24 compared with baseline serum creatinine). Rejection was reversed in 86 (98%) patients. Graft survival at 1 year after OKT3 therapy was 87.5% (77 of 88). At a mean follow-up of 38 months, 8 patients had died and 26 grafts were lost. The mean serum creatinine level in the 64 patients with a functioning graft was 1.76 mg/dl (range, 0.8-4.0 mg/dl) at the last follow-up. CONCLUSION: OKT3 when utilized as first-line therapy reversed 98% of the acute rejection episodes, with a 1-year post-OKT3 graft survival of 87.5%.

Acute Disease↗
PubMed1997

Primary care of patients with renal transplants.

The number of renal transplant recipients in the community continues to rise due to improved organ and patient survival. With increasing emphasis on primary care, more organ transplant recipients are being cared for by primary care physicians. This article outlines the management of renal transplant recipients and reviews the problems unique to this group of patients.

Cadaver↗
PubMed1997

Clinical and economic outcomes of expanded criteria donors in renal transplantation.

Although graft and patient survival rates were similar between recipients of kidneys from ECDs and non-ECDs, transplantation with organs from ECDs was significantly more expensive. Multivariate analysis using stepwise linear regression demonstrated length of stay to be a strong proxy for total hospital costs. Inherent tensions between the overall good clinical outcomes associated with the use of ECDs in terms of graft survival and the markedly increased costs seen with these organs are evident.

Age Factors↗
PubMed1997

The donor supply.

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Age Factors↗
PubMed1997

An update on new immunosuppressive drugs undergoing preclinical and clinical trials: potential applications in organ transplantation.

Recent advances in immunobiology and immunopharmacology have led to a better understanding of the actions of immunosuppressive drugs. Over the past 2 years, a number of new agents have been approved for use in solid organ transplant recipients. In addition, new immunosuppressive agents are being tested in preclinical and clinical trials, leading to the promise of an exciting future in organ transplantation. This report reviews the mechanisms of action and the potential future role of these agents in clinical transplantation.

Humans↗
PubMed1997

Impact of ganciclovir prophylaxis on cytomegalovirus infection in recipients of cadaveric renal allografts.

Cytomegalovirus (CMV) infection is a major cause of morbidity and occasionally of mortality in immunosuppressed allograft recipients. At the University of Cincinnati Medical Center, ganciclovir has been administered for the prevention of CMV infection since July 1992. Forty-six recipients of cadaveric renal allografts (Group I) received ganciclovir at a dose of 2.5 or 5 mg/kg/day (adjusted for renal function) for 14-21 days, during induction treatment and during antirejection treatment with monoclonal or polyclonal antilymphocyte preparations. In this retrospective study, these 46 patients were compared with 77 recipients of cadaveric renal allografts transplanted prior to July 1992 (Group II) for the prevalence, severity and time of CMV occurrence after transplantation. CMV diagnosis was based on clinical evaluation and was confirmed by blood cultures, CMV antigen immunofluorescence assay and/or histology. Patients were stratified according to CMV serology (+) or (-) in donor and recipient. CMV infection developed in 16 of 46 (35%) patients in Group I vs. 27 of 77 (35%) patients in Group II (p = 0.97). A total of 25 episodes of CMV infection occurred in Group I compared to 44 in Group II (p = 0.76). CMV infection was diagnosed an average of 97.4 days after transplant in Group I compared to 48.3 days in Group II (p = 0.0003). Tissue-invasive CMV infection occurred in 3 patients in Group I (19%) vs. 12 in Group II (44%) (p = 0.5). In conclusion, ganciclovir prophylaxis resulted in a delayed onset of clinical CMV infection with a trend towards less severe infection in patients treated with antilymphocyte antibody preparations.

Adult↗
PubMed1997

Causes of renal allograft loss in black vs. white transplant recipients in the cyclosporine era.

Black renal transplant recipients have a higher rate of allograft loss than white recipients. From 1 January 1984 to 1 January 1995, 463 transplants were performed at a single center and followed for a mean duration of 71 months. The causes of graft loss for white and black recipients, their age, gender, retransplantation rate, organ source, and HLA matching were compared. In the 150 black and 313 white recipients, graft loss rates in the first year were 20% in both groups, while after 1 yr there were 42 (28%) graft losses in blacks vs. 62 (20%) in whites (log-rank test p = 0.04). All diagnoses deemed causative of allograft loss were confirmed by biopsy. Chronic rejection resulting in graft loss occurred in 15% (n = 23) of black recipients compared to only 7% (n = 22) of white recipients (p = 0.002). There were no significant differences in the rate of death with a functioning kidney or other causes of graft loss between the two groups. A significant increase in HLA mismatches was noted in black recipients of cadaveric grafts compared to whites, but there was no difference between races in the rate of graft loss due to acute rejection. While the rate of graft survival remains lower in black recipients in the cyclosporine era, this is due entirely to late graft loss after 1-yr post-transplant due to chronic rejection.

Acute Disease↗
PubMed1997

Expanding the donor pool.

Advances in techniques and the development of new immunosuppressive drugs have made it possible to transplant a large number of patients throughout the world. However, the shortage of cadaveric organ donors remains the major obstacle for the full development of organ transplantation, imposing a severe limit to the number of patients who could benefit from this therapy. Although transplants save thousands of lives and transform the quality of life of thousands more, many people will die or remain on renal replacement therapy because the organ supply falls drastically short of actual demand. In the US, the number of organ donors has increased approximately 20% over the past 5 years, but this increase has been brought about largely by the use of older donors and other donors considered by some to be marginal. In the 6 years from 1988 to 1994, the waiting list for kidneys grew by 76% in the US. By the end of August 1996, there were 33,339 patients registered for kidneys on the national transplant waiting list. This report examines the issue of the elderly donor, the role of living-unrelated kidney transplantation, and proposes various strategies to enhance procurement of cadaver kidneys.

Adolescent↗
PubMed1997

Combined kidney-pancreas and parathyroid transplantation: a case report.

We report the first successful multiorgan kidney-pancreas and parathyroid tissue transplant in a patient with autoimmune polyglandular syndrome and medullary cystic disease. Successful transplantation included quadruple drug induction therapy consisting of antithymocyte globulin, azathioprine, cyclosporine and prednisone. All three grafts are functioning 2 yr after transplantation.

Adult↗
PubMed1996

Diabetic nephropathy after renal transplantation. Clinical and pathologic features.

The histologic diagnosis of diabetic glomerulosclerosis was made in 14 renal transplant recipients. All 14 had insulin-dependent diabetes mellitus, which was the original cause of end-stage renal disease in 12; one patient had membranoproliferative glomerulonephritis and another patient had membranous nephropathy as the cause of end-stage renal disease. Insulin-dependent diabetes mellitus was diagnosed at an average age of 18.5 years (range, 8-41 years), and the mean duration of diabetes prior to transplantation was 15 years (range, 2-25 years). All patients were recipients of first kidney transplants (six living related donors and eight cadavers). The histologic diagnosis of diabetic glomerulosclerosis was made on average, 97 months after transplantation (range 41-154 months). All 14 patients had proteinuria (mean 5.3 g/24 hr; range 1.1-12 g/24 hr) and renal dysfunction (mean serum creatinine level, 2.8 mg/dl). Patient and graft survival rates at 1 year, 5 years, and 10 years after transplantation were 100%, 92%, and 59%, and 100%, 92%, and 34%, respectively. Graft failure was due to diabetic nephropathy in seven patients, diabetic nephropathy and membranous nephropathy in one patient, and death due to a cerebrovascular accident in one patient. A total of five patients are alive with a functioning kidney. Of the eight patients who returned to dialysis, four are alive, three remain on dialysis, and 1 had a combined kidney and pancreas transplant. Histologic findings were as follows: 9/14 had moderate or severe diffuse glomerular basement membrane thickening and 2/14 had nodular glomerulosclerosis. Arteriolar lesions were prominent in all cases and was graded moderate or severe in 11 cases. The development of allograft diabetic nephropathy is associated with a high rate of allograft failure.

Adult↗
PubMed1996

Rescue therapy with tacrolimus after combined kidney/pancreas and isolated pancreas transplantation in patients with severe cyclosporine nephrotoxicity.

This study details 11 pancreas transplant recipients (10 combined kidney and pancreas and 1 pancreas after kidney) who were converted to tacrolimus (FK506) due to acute severe cyclosporine nephrotoxicity in 8 cases and persistent rejection with cyclosporine toxicity in three cases. Arteriolopathy was documented by renal histology in all cases. Cyclosporine was discontinued for 24 hr immediately prior to initiation of tacrolimus. Tacrolimus was started orally at 0.1 mg/kg twice daily with dose adjustments to maintain whole blood trough levels of 8-15 ng/mL by IMx. Tacrolimus was initiated a mean of 14.5 months (range 1-81) after pancreas transplantation. The mean serum creatinine level had increased to 2.9 mg/dl from 1.0 mg/dl at the diagnosis of cyclosporine arteriolopathy (P=0.003). The mean serum creatinine and blood glucose levels at the time of initiation of tacrolimus were 2.1 mg/dl and 104 mg/dl, respectively. Serum creatinine was 1.7 mg/dl, 1.9 mg/dl, 1.8 mg/dl, and 1.7 mg/dl after 1, 2, 3, and 6 months of tacrolimus therapy, respectively; ANOVA (P = 0.02). The corresponding blood glucose levels were 117 mg/dl, 112 mg/dl, 109 mg/dl, and 116 mg/dl, respectively (P=NS). Normal C-peptide levels were present before (5.9 ng/ml) and after (6.2 ng/ml), the initiation of tacrolimus therapy (P=NS), and mean HbA1C was 6.1% before and 6.3% after tacrolimus therapy, (P=NS). There were 4 episodes of acute rejection, 3 responded to intravenous methylprednisolone, and 1 required OKT3 during tacrolimus therapy. Reversible tacrolimus nephrotoxicity was noted in three patients without any evidence of progressive vasculopathy. All 11 patients are alive, and 10/11 kidney and pancreas grafts are functioning with a mean follow-up of 7.7 months (range 5-10). In this study, conversion from cyclosporine to tacrolimus in kidney and pancreas recipients resulted in improvement and stabilization of renal function while maintaining stable blood glucose, C peptide, and HbA1C levels.

Administration, Oral↗