Transplantation using marginal living donors.
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Humans↗
Biomedical subjects
Arthur J Matas
Publications and source records attributed to Arthur J Matas.
Urinary beta2-microglobulin is associated with acute renal allograft rejection.
BACKGROUND: Identifying urinary biomarkers associated with acute rejection (AR) of kidney allografts could improve recipient care by allowing AR to be diagnosed noninvasively and treated earlier. We attempted to identify novel biomarkers associated with AR by analyzing urinary proteins by using matrix-associated laser desorption ionization time-of-flight mass spectroscopy (MALDI-TOF MS). METHODS: Using MALDI-TOF MS, we analyzed urine samples from 30 renal allograft recipients with biopsy-proven AR, 15 allograft recipients without AR, preoperative samples from 29 kidney donors, and 10 subjects with proteinuric native kidney disease. RESULTS: In samples obtained at the time of AR, we identified a protein peak at 11.7 kd that correlated strongly with AR. In regard to its predictive power for AR, this protein peak showed sensitivity of 83.3%, specificity of 80%, positive predictive value of 89%, and negative predictive value of 70.6%, suggesting that this protein is highly associated with AR. We identified this peak as being beta2-microglobulin. This was validated by using enzyme-linked immunosorbent assay, which documented the presence of high urinary beta2-microglobulin levels in subjects with AR. CONCLUSION: Beta2-microglobulin could be a strong biomarker for AR if used in conjunction with other biomarkers, producing an AR-specific urinary protein signature. This possibility must be confirmed in a larger cohort of kidney transplant recipients.
Acute Disease↗
Persistent, asymptomatic, microscopic hematuria in prospective kidney donors.
BACKGROUND: Asymptomatic, microscopic hematuria is seen in 8-21% of the general population, has a good prognosis, and is generally not an indication for kidney biopsy. But whether it should preclude kidney donation is unclear. METHODS: Of 512 consecutive prospective donors, 14 (2.7%) continued to have asymptomatic, microscopic hematuria over 1 month. If the medical history, physical examination, and computerized tomographic angiography were unremarkable, and if they still wished to donate, a kidney biopsy was performed. RESULTS: In two prospective donors, hematuria resolved after treatment for urinary tract infection; two others declined donation and were referred to their primary care provider. Kidney biopsy in the remaining 10 showed: two normal; four thin basement membrane nephropathy (TBMN); one nonhomogeneous basement membrane abnormalities; one IgA nephropathy, 5 of 16 glomeruli globally sclerotic; one in a patient with a family history of Schimke's Syndrome, 7 of 30 glomeruli globally sclerotic; and one TBMN and early hypertensive changes without systemic hypertension. Only 4 of the 10 who underwent kidney biopsy donated (two normal, two TBMN). CONCLUSIONS: Kidney abnormalities are common in young, otherwise healthy, prospective kidney donor candidates with persistent, asymptomatic, microscopic hematuria. A kidney biopsy is often abnormal and aids in the decision-making process.
Adolescent↗
The importance of innovative efforts to increase organ donation.
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Humans↗
A multicenter pilot study of early (4-day) steroid cessation in renal transplant recipients under simulect, tacrolimus and sirolimus.
This study presents the first prospective multicenter study assessing sirolimus-based immunosuppression with early (4-day) corticosteroid withdrawal (CSWD) in renal transplantation. Immunosuppression included: anti-IL-2 receptor antibody and tacrolimus/sirolimus. Inclusion criteria included adult primary recipients. Exclusion criteria included: (i) African Americans, (ii) current PRA >50%, (iii) multiple organ transplants, (iv) WBC < 3000 cells/microL and (v) fasting hypercholesterolemia/hypertriglyceridemia. The primary endpoints were acute rejection and the proportion of patients off corticosteroids. Seventy-seven patients were enrolled: mean age of 49.7 +/- 12 years. Transplants included: cadaveric (26%) and living donor (74%). Patient and graft survival were 100%. Biopsy proven acute rejection occurred in 13%; presumptive rejection in 10.5%. Banff grades included: IA (seven patients), IB (one patient), IIA (one patient) and IIB (one patient). Renal function at 1 year: serum creatinine (1.18 +/- 0.06 mg/dL). Mean weight gain was minimal at 1 year: 3 +/- 2 kg/patient. Mild increases in total, LDL and HDL cholesterol were observed and new antilipid agent use occurred in 26 patients. In conclusion, early CSWD under tacrolimus/sirolimus-based immunosuppression in selected, low-risk renal transplant recipients provides: (i) excellent patient and graft survival, (ii) good renal function, (iii) reduced hyperlipidemia and antilipid agent use and (iv) low acute rejection rates.
Adrenal Cortex Hormones↗
Long-term deterioration of kidney allograft function.
Although long-term survival after kidney transplantation is critically dependent on maintaining stable allograft function, few studies have examined renal allograft function over time. Using pooled data from 10 278 consecutive transplants at five centers, we calculated slopes of estimated glomerular filtration rates (eGFR) measured after 1, 6 and 12 months in 9515, 8861 and 7359 patients surviving > or =1, > or =6 and > or =12 months, respectively. Slopes of eGFR progressively diminished for patients transplanted during 1984-1989, 1990-1993, 1994-1998 and 1999-2002 (analysis of variance p < 0.0001 and p = 0.1245 for slopes measured after 1 and 6 months, respectively). Slopes measured after 12 months were less in the most recent era: -2.2 +/- 7.2 mL/min/1.73 m(2)/year, -2.3 +/- 6.6 mL/min/1.73 m(2)/year, -2.4 +/- 7.4 mL/min/1.73 m(2)/year and -1.4 +/- 10.9 mL/min/1.73 m(2)/year, respectively, p = 0.0058. Slopes measured after 1, 6 and 12 months each were less for transplantations during 1999-2002, after adjusting for multiple transplantation characteristics (p < 0.0001). Similarly, in Cox proportional hazards analysis, the risk (95% CI) for a 25% reduction in eGFR was 0.92 (0.85-1.01), p = 0.0736 during 1990-1994; 0.94 (0.82-1.08), p = 0.4111 during 1995-1998 and 0.78 (0.64-0.95), p = 0.0110 during 1999-2002 (compared to 1984-1989). We conclude that the rate of decline in allograft function after kidney transplantation has improved, suggesting that stable, long-term function may be achievable.
Adolescent↗
A prospective randomized trial of steroid-free maintenance regimens in kidney transplant recipients--an interim analysis.
We compared three maintenance immunosuppressive regimens in a rapid discontinuation of prednisone protocol. From March 1, 2001, through December 31, 2003, 239 first and second kidney transplant recipients (166 LD; 73 DD) were randomized. All recipients were treated with Thymoglobulin; all received steroids intraoperatively and for 5 days postoperatively. Randomization was to cyclosporine-mycophenolate mofetil (n = 85); high-level tacrolimus (TAC) (8-12 ng/mL)-low-level sirolimus (SRL) (3-7 ng/mL) (n = 72); or low-level TAC (3-7 ng/mL)-high-level SRL (8-12 ng/mL) (n = 82). We found no difference at 24 months between groups in patient, graft, death-censored graft, or acute rejection-free graft survival, or in kidney function. Wound complications were more common in SRL-treated recipients (p = 0.02); we found no other differences between groups in complication rates. Our data suggest that excellent patient and graft survival and low rejection rates can be obtained using a variety of maintenance protocols without prednisone.
Antilymphocyte Serum↗
Reproduction and transplantation: report on the AST Consensus Conference on Reproductive Issues and Transplantation.
It has been almost 50 years since the first child was born to a female transplant recipient. Since that time pregnancy has become common after transplantation, but physicians have been left to rely on case reports, small series and data from voluntary registries to guide the care of their patients. Many uncertainties exist including the risks that pregnancy presents to the graft, the patient herself, and the long-term risks to the fetus. It is also unclear how to best modify immunosuppressive agents or treat rejection during pregnancy, especially in light of newer agents available where pregnancy safety has not been established. To begin to address uncertainties and define clinical practice guidelines for the transplant physician and obstetrical caregivers, a consensus conference was held in Bethesda, Md. The conferees summarized both what is known and important gaps in our knowledge. They also identified key areas of agreement, and posed a number of critical questions, the resolution of which is necessary in order to establish evidence-based guidelines. The manuscript summarizes the deliberations and conclusions of the conference as well as specific recommendations based on current knowledge in the field.
Female↗
Prednisone-free maintenance immunosuppression-a 5-year experience.
Concern persists that prednisone-free maintenance immunosuppression in kidney transplant recipients will be associated with an increase in late allograft dysfunction and graft loss. We herein report 5-year follow-up of a trial of prednisone-free maintenance immunosuppression. From October 1, 1999, through January 31, 2005, at our center, 589 kidney transplant recipients were treated with a protocol incorporating discontinuation of their prednisone on postoperative day 6. At 5 years, actuarial patient survival was 91%; graft survival, 84%; death-censored graft survival, 92%; acute rejection-free graft survival, 84% and chronic rejection-free graft survival, 87%. The mean serum creatinine level (+/-SD) at 1 year was 1.6 +/- 0.6; at 5 years, 1.7 +/- 0.8. In all, 86% of kidney recipients with functioning grafts remain prednisone-free as of April 30, 2005. As compared with historical controls, recipients on prednisone-free maintenance immunosuppression had a significantly lower rate of a number of complications, including cataracts (p < 0.001), posttransplant diabetes mellitus (p < 0.001), avascular necrosis (p = 0.001), and fractures (p = 0.004). We conclude that prednisone-related side effects can be minimized in a protocol incorporating prednisone-free maintenance immunosuppression. Five-year graft outcome remains good.
Anti-Infective Agents↗
Rapid discontinuation of prednisone in higher-risk kidney transplant recipients.
Prednisone-minimization protocols have been successful in low-risk recipients. We report on the use of a protocol incorporating rapid discontinuation of prednisone in a cohort of kidney transplant recipients (n = 79) at increased immunologic risk. Our data suggests that such recipients should not be excluded from prednisone-minimization protocols.
Humans↗
Medication noncompliance: another iceberg's tip.
After renal transplantation, immunosuppressive medications must be taken long-term to avoid acute rejection and the cascade of events leading to "chronic allograft dysfunction" and loss. In the past, when posttransplant immunosuppression was limited to azathioprine and prednisone, acute rejection episodes were common, and it was difficult to identify the impact of medication noncompliance. However, with more potent and effective drugs, acute rejection is uncommon, and medication noncompliance emerges as an increasingly important factor in the outcome of solid-organ transplantation. Recent studies have clearly demonstrated that medication noncompliance leads to an increased incidence of acute rejection, chronic rejection, and graft loss. Today, although a number of questions remain unanswered, new methodologies, such as electronic monitors, provide opportunities to study medication noncompliance and its risk factors, and the potential for earlier intervention to improve clinical outcomes.
Graft Rejection↗
Plasma homocysteine levels in living kidney donors before and after uninephrectomy.
An increased prevalence of hyperhomocysteinemia has been observed among patients with end-stage renal disease, and numerous studies have demonstrated that kidney function is one of the most important determinants of plasma total homocysteine (tHcy) concentration. In an effort to understand the mechanism of hyperhomocysteinemia in renal disease, we chose, as our model, living kidney donors who had undergone uninephrectomy. We studied 10 living kidney donors and measured fasting plasma tHcy, plasma creatinine, folate, vitamins B(12) and B(6), and high-sensitivity C-reactive protein (hsCRP) 24 hours before nephrectomy and 2 days, 6 weeks, and 6 months after nephrectomy compared to the values 24 hours before nephrectomy. Mean fasting tHcy and creatinine concentrations were significantly higher in donors 2 days, 6 weeks and 6 months after nephrectomy they were 24 hours before nephrectomy. Both the increases in tHcy levels 2 days after nephrectomy and subsequent decreases 6 weeks and 6 months after are paralleled by the changes in plasma creatinine values, although neither returned to its presurgery value. Decreases in tHcy are significantly correlated with decreases in creatinine values. The B vitamins were unchanged, and the hsCRP level was increased 2 days after surgery but had returned to the baseline level after 6 weeks. We conclude that tHcy and creatinine levels parallel each other after uninephrectomy and that the gradual decrease in tHcy is accounted for by hypertrophy of the remaining kidney. Our results, the first to be obtained from living kidney donors, support the hypothesis that renal metabolism of tHcy is the mechanism responsible for the correlation between renal function and plasma tHcy level.
Adult↗
Payment for living donor (vendor) kidneys: a cost-effectiveness analysis.
The supply of kidneys does not meet the demand. As a consequence, the waiting time for a cadaver kidney continues to lengthen, and there is renewed debate about payment for living donors. To facilitate this debate, we studied what amount of payment would be cost-effective for society, i.e. what costs would be saved (if any) by removing a patient from the waiting list using a paid (living unrelated: LURD) donor-vendor. A Markov model was developed to calculate the expected average cost and outcome benefits of increasing the organ supply and reducing waiting times by adding paid LURD organs to the available pool. We found that a LURD transplant saved $94,579 (US dollars, 2002), and 3.5 quality-adjusted life years (QALYs) were gained. Adding the value of QALYs, a LURD transplant saved $269 319, assuming society values additional QALYs from transplantation at the rate paid per QALY while on dialysis. At a minimum, a vendor program would save society >$90,000 per transplant and provides QALYs for the ESRD population. Thus, society could break even while paying $90,000/kidney vendor.
Cost-Benefit Analysis↗
Long-term immunosuppression, without maintenance prednisone, after kidney transplantation.
BACKGROUND: Concern exists that prednisone-free maintenance immunosuppression in kidney transplant recipients will increase acute and/or chronic rejection. METHODS: From October 1, 1999, through February 29, 2004, at our center, 477 kidney transplant recipients (341 living donor, 136 cadaver) discontinued prednisone on postoperative day 6, per our protocol. Immunosuppression consisted of polyclonal antibody (Thymoglobulin) for 5 days, prednisone intraoperatively and for 5 days, a calcineurin inhibitor, and either sirolimus or mycophenolate mofetil. We compared outcome with that of historical controls who did not discontinue prednisone. RESULTS: The recipients on prednisone-free maintenance immunosuppression had excellent 4-year actuarial patient survival (92%), graft survival (90%), acute rejection-free graft survival (86%), and chronic rejection-free graft survival (95%). The mean serum creatinine level (+/- SD) at 1 year was 1.6 +/- 0.6; at 4 years, 1.6 +/- 0.6. We noted that 8% of recipients had cytomegalovirus (CMV) disease; 4.5%, fractures; 2.8%, cataracts; 1%, posttransplant diabetes; 0.2%, avascular necrosis; 0.2%, posttransplant lymphoproliferative disease; and 0%, polyomavirus. In all, 85% of kidney recipients with functioning grafts remain prednisone-free as of April 1, 2004. As compared with historical controls, the recipients on prednisone-free maintenance immunosuppression had better patient (P = 0.02) and graft survival (P < 0.0001) and lower rates of acute (P = 0.0004) and chronic (P = 0.02) rejection. In addition, they had a significantly lower rate of CMV disease (P < 0.0001), cataracts (P < 0.0001), posttransplant diabetes (P < 0.0001), and avascular necrosis (P = 0.0003). CONCLUSIONS: Prednisone-related side effects can be minimized without maintenance immunosuppression; our prednisone-free recipients do not have increased acute or chronic rejection.
Adult↗
Outcome at 3 years with a prednisone-free maintenance regimen: a single-center experience with 349 kidney transplant recipients.
Historically, late steroid withdrawal after kidney transplants has been associated with an increased rejection rate. Recently, low rejection rates have been reported for recipients treated with complete avoidance or rapid elimination of steroids. However, follow-up has been short. We herein report on 3-year outcome in recipients whose prednisone was rapidly eliminated and who were maintained on a steroid-free regimen. From 10/1/1999 through 5/1/2003, 349 recipients (254 LD, 95 CAD; 319 in first 30 s) were immunosuppressed with polyclonal antibody (Thymoglobulin), a calcineurin inhibitor, either mycophenolate mofetil or sirolimus, and rapid discontinuation of prednisone. Actuarial 3-year patient survival was 95%; graft survival, 93%. Acute rejection-free graft survival at 1 year was 94%; at 3 years, 92%. There was no difference between LD and CAD. At 2 years, the mean (+/- SE) serum creatinine level for LDs was 1.6 +/- 0.5 mg/dL; for CAD, 1.6 +/- 0.4 mg/dL. We have no new cases of PTLD or avascular necrosis; 22 recipients (6%) developed CMV. Currently, 84% of recipients remain prednisone-free. We conclude that excellent 3-year patient and graft survival can be achieved without maintenance prednisone. With such a protocol, steroid-related side-effects are minimal.
Antilymphocyte Serum↗
Twenty-two nondirected kidney donors: an update on a single center's experience.
At the University of Minnesota, we have defined 'nondirected donation' as organ donation by a volunteer who offered to donate an organ to anyone on the cadaver waiting list. From October 1, 1997, through October 31, 2003, we have had 360 inquiries about nondirected donation, have completed 42 detailed nondirected donor (NDD) evaluations for kidney donation, and have performed 22 NDD transplants. We herein review our program policies and how they have evolved, describe our evaluation and the motivation of our potential donors, summarize the outcome of NDD transplants, and raise issues requiring further attention and study. Our experience continues to support nondirected donation for kidney transplants.
Academic Medical Centers↗
Payment for living kidney donors (vendors) is not an abstract ethical discussion occurring in a vacuum.
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Algorithms↗
The case for living kidney sales: rationale, objections and concerns.
Currently, potential kidney transplant candidates are dying on the waiting list. One potential solution would be a regulated system of living kidney sales (with safeguards to protect the vendor). Potential objections and practical concerns are discussed.
Commerce↗