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1.
Transplantation ; 101(10): 2590-2598, 2017 10.
Article in English | MEDLINE | ID: mdl-28376034

ABSTRACT

BACKGROUND: Short- and intermediate-term results have been reported after rapid discontinuation of prednisone (RDP) in kidney transplant recipients. Yet there has been residual concern about late graft failure in the absence of maintenance prednisone. METHODS: From October 1, 1999, through June 1, 2015, we performed a total of 1553 adult first and second kidney transplants-1021 with a living donor, 532 with a deceased donor-under our RDP protocol. We analyzed the 15-year actuarial overall patient survival (PS), graft survival (GS), death-censored GS (DCGS), and acute rejection-free survival (ARFS) rates for RDP compared with historical controls on maintenance prednisone. RESULTS: For living donor recipients, the actuarial 15-year PS rates were similar between groups. But RDP was associated with increased GS (P = 0.02) and DCGS (P = 0.01). For deceased donor recipients, RDP was associated with significantly better PS (P < 0.01), GS (P < 0.01) and DCGS (P < 0.01). There was no difference between groups in the rate of acute or chronic rejection, or in the mean estimated glomerular filtration rate at 15 years. However, RDP-treated recipients had significantly lower rates of avascular necrosis, cytomegalovirus, cataracts, new-onset diabetes after transplant, and cardiac complications. Importantly, for recipients with GS longer than 5 years, there was no difference between groups in subsequent actuarial PS, GS, and DCGS. CONCLUSIONS: In summary, at 15 years postkidney transplant, RDP did not lead to decreased in PS or GS, or an increase in graft dysfunction but as associated with reduced complication rates.


Subject(s)
Forecasting , Graft Rejection/drug therapy , Graft Survival/drug effects , Kidney Transplantation , Prednisone/therapeutic use , Transplant Recipients , Withholding Treatment , Adult , Drug Administration Schedule , Female , Follow-Up Studies , Glucocorticoids/therapeutic use , Graft Rejection/mortality , Humans , Male , Middle Aged , Minnesota/epidemiology , Survival Rate/trends , Tissue Donors
2.
Clin Transplant ; 31(1)2017 01.
Article in English | MEDLINE | ID: mdl-27740731

ABSTRACT

Transplant programs inform potential donors that they should be able to return to normal activities within ~2 weeks and to work by 6 weeks after laparoscopic nephrectomy. We studied actual time. Between 10/2004 and 9/2014, 911 donors having laparoscopic nephrectomy were surveyed 6 months post-donation. Surveys asked questions specific to their recovery experience, including time to return to normal activities and work and a description of their recovery time relative to pre-donation expectations. Of the 911, 646 (71%) responded: mean age at donation was 43.5±10.6 years; 65% were female, 95% were white, 51% were biologically related to their recipient, and 83% reported education beyond high school. Of the 646 respondents, a total of 35% returned to normal activities by 2 weeks post-donation; 79% by 4 weeks post-donation; 94% by 5-6 weeks; however, 6% took >6 weeks. Of the 646, 551 (85%) were working for pay; of these, mean time to return to work was 5.3±2.8 weeks; median, 5 weeks. Of the 551, a total of 14% returned to work in 1-2 weeks, 46% by 3-4 weeks, and 76% by 5-6 weeks. Importantly, 24% required >6 weeks before returning to work with the highest rates for donors in manual labor or a skilled trade. Significantly longer return to work was reported by females (vs males; P=.01), those without (vs those with) post-high school education (P=.010, those with longer hospital stay (P=.01), and those with a postoperative complication (P=.02). Of respondents, 37% described their recovery time as longer than expected. During the donor informed consent process, additional emphasis on realistic expectations around recovery to baseline activities and return to work is warranted.


Subject(s)
Activities of Daily Living , Kidney Failure, Chronic/surgery , Kidney Transplantation , Laparoscopy/methods , Living Donors , Nephrectomy , Tissue and Organ Harvesting/methods , Adult , Female , Follow-Up Studies , Humans , Male , Prognosis
3.
Pediatr Transplant ; 20(7): 939-945, 2016 Nov.
Article in English | MEDLINE | ID: mdl-27712016

ABSTRACT

The association of blood transfusions with GS after pediatric KTx is unclear. We retrospectively analyzed blood transfusions post-KTx and subsequent outcomes. Between 1984 and 2013, 482 children (<18 years of age) underwent KTx at our center. Recipient demographics, outcomes and transfusion data were collected. Cox regression with post-KTx blood transfusion as a time-dependent covariate was performed to model the impact of blood transfusion on outcomes. Of the 208 (44%) that were transfused, 39% had transfusion <1 month post-KTx; 48% >12 months. Transfused and non-transfused recipients were not significantly different. In univariate and multivariate analyses, there was no difference between transfused and non-transfused recipient patient survival, antibody-mediated and ACR, and DSA free survival. Transfusions <1 month post-KTx did not impact DCGS (P=NS). Patients transfused >12 months post-KTx had significantly lower 12 month eGFR (compared to non-transfused) and worse subsequent DCGS. Post-KTx blood transfusions have increased in pediatric KTx over time but have no negative association with rejection or DSA production. DCGS is unaffected by transfusion within first month. Transfusions after the first year occur in patients with more advanced chronic kidney disease and are associated with significantly worse DCGS.


Subject(s)
Blood Transfusion/statistics & numerical data , Kidney Transplantation , Renal Insufficiency/surgery , Adolescent , Child , Child, Preschool , Delayed Graft Function , Female , Glomerular Filtration Rate , Graft Survival , Humans , Immunosuppression Therapy , Kidney Transplantation/adverse effects , Male , Postoperative Complications , Proportional Hazards Models , Renal Insufficiency/mortality , Retrospective Studies , Time Factors , Treatment Outcome , Young Adult
4.
Clin Transplant ; 27(3): 472-80, 2013.
Article in English | MEDLINE | ID: mdl-23647497

ABSTRACT

Hypertension (HTN) is common in pediatric recipients following kidney transplantation (KT). We retrospectively assessed the impact of HTN on long-term (>10-yr) outcomes in pediatric KT recipients (aged < 18 yr) at our center. Two hundred and ninety-three pediatric KT recipients (83% living donor [LD]) with graft survival (GS) for ≥5 yr were studied. HTN was defined by antihypertensive medication use at five yr post-KT. One hundred and sixty (55%) recipients did not have HTN, and 133 (45%) had HTN at five yr post-KT. There were no differences in actuarial patient survival between cohorts. Actuarial GS at 15 and 20 yr was 68% and 53% for recipients without HTN, and 53% and 33% for recipients with HTN (p = 0.006). Among LD recipients using one antihypertensive, GS at 15 yr was 100% for those using an angiotensin-converting enzyme inhibitor (ACEI) and 44% for those not using an ACEI (p = 0.04). Among these recipients, HTN treated with no ACEI was a significant risk factor for graft failure at >5 yr (hazard ratio [HR] = 2.5, p = 0.02), but HTN treated with an ACEI was not (HR = 0.6, p = 0.7). HTN at five yr post-KT is associated with poorer long-term GS in pediatric recipients, but ACEI therapy may enable better outcomes and should be studied further.


Subject(s)
Graft Rejection/mortality , Graft Survival , Hypertension/mortality , Kidney Diseases/complications , Kidney Transplantation/adverse effects , Adolescent , Antihypertensive Agents/therapeutic use , Child , Child, Preschool , Female , Follow-Up Studies , Graft Rejection/drug therapy , Graft Rejection/etiology , Humans , Hypertension/drug therapy , Hypertension/etiology , Kidney Diseases/mortality , Kidney Diseases/surgery , Kidney Transplantation/mortality , Male , Prognosis , Retrospective Studies , Risk Factors , Survival Rate , Time Factors
5.
Pediatr Transplant ; 16(7): 704-10, 2012 Nov.
Article in English | MEDLINE | ID: mdl-22574837

ABSTRACT

Recurrent disease is the fourth most common cause of graft loss (GL) in pediatric KTx recipients. We studied the incidence of recurrent disease and GL due to recurrent disease in pediatric KTx recipients on a RDP protocol. Between 2002 and 2010, we performed 74 KTxs in patients aged 5-18 yr using an RDP protocol, 25 (34%) were at risk of recurrence of primary disease. Outcomes were compared to 69 historical controls (18 [26%] at risk of recurrence), KTx between 1996 and 2000. Follow-up period was 39 ± 25 months in RDP and 124 ± 38 months in controls. The incidence of recurrent disease at three yr post-KTx was 16% in RDP and 28% in controls (p = NS). Mean time to recurrent disease was 22 ± 26 months in RDP and 46 ± 48 months in controls (p = 0.54). Nine (12%) grafts were lost in the RDP group (1-recurrence) and 32 (46%) in the control group (4-recurrence). Time to GL was 85 months in the RDP recipient and 46 ± 21 months in controls. An RDP protocol in pediatric KTx recipients may not be associated with increased risk of graft loss due to recurrent disease.


Subject(s)
Kidney Transplantation/methods , Prednisone/pharmacology , Renal Insufficiency/drug therapy , Renal Insufficiency/therapy , Adolescent , Child , Female , Graft Rejection , Graft Survival , Humans , Immunosuppressive Agents/therapeutic use , Male , Prednisone/administration & dosage , Recurrence , Retrospective Studies , Risk , Time Factors
6.
Clin J Am Soc Nephrol ; 7(3): 494-503, 2012 Mar.
Article in English | MEDLINE | ID: mdl-22282482

ABSTRACT

BACKGROUND AND OBJECTIVES: Rapid discontinuation of prednisone after kidney transplantation potentially allows for minimization of steroid-related side effects. Although intermediate-term data with rapid discontinuation of prednisone have been promising, concern still exists regarding long-term outcomes. The 10-year experience is reported herein. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Between October 1, 1999 and December 31, 2010, 1241 adult primary kidney transplants (791 living donor and 450 deceased donor) were performed using a protocol in which prednisone is discontinued after postoperative day 5. The 10-year actuarial recipient and graft survival rates and prednisone-related side effects were studied. RESULTS: Ten-year actuarial patient survival was 71% for living donor transplants and 62% for deceased donor transplants; 10-year graft survival was 61% for living donor transplants and 51% for deceased donor transplants, and was comparable to 10-year Scientific Registry of Transplant Recipients national data. Ten-year death-censored graft survival was 79% for living donor transplants and 80% for deceased donor transplants. Ten-year acute rejection rates were 25% for deceased donor transplants and 31% for living donor transplants; 10-year chronic rejection (interstitial fibrosis/tubular atrophy) rates were 39% for deceased donor transplants and 47% for living donor transplants. For nondiabetic recipients of living donor or deceased donor allografts, the incidence of new-onset diabetes was significantly lower than in historical controls on prednisone (P<0.001). We also found significantly reduced rates of cataracts, avascular necrosis, and cytomegalovirus infection in some subgroups. CONCLUSIONS: Prednisone-related side effects can be minimized in a protocol incorporating rapid discontinuation of prednisone for maintenance immunosuppression. Ten-year patient and graft outcomes remain acceptable.


Subject(s)
Graft Rejection/prevention & control , Graft Survival/drug effects , Immunosuppressive Agents/administration & dosage , Kidney Transplantation , Prednisone/administration & dosage , Adult , Drug Administration Schedule , Female , Graft Rejection/immunology , Humans , Immunosuppressive Agents/adverse effects , Kaplan-Meier Estimate , Kidney Transplantation/adverse effects , Kidney Transplantation/immunology , Kidney Transplantation/mortality , Living Donors , Male , Middle Aged , Minnesota , Prednisone/adverse effects , Risk Assessment , Risk Factors , Time Factors , Treatment Outcome
7.
Clin Transplant ; 26(1): E7-11, 2012.
Article in English | MEDLINE | ID: mdl-22017317

ABSTRACT

Individuals with kidneys having ≥ 2 arteries appear to have an increased incidence of hypertension. Whether kidney donors in whom the remaining kidney has ≥ 2 arteries are at increased risk of hypertension is unknown. Therefore, we studied 3685 kidney donors to determine whether donors left with a kidney having ≥ 2 arteries were at increased risk of hypertension, impaired renal function, or death. Cohorts were assigned based on our practice pattern and the anatomy of the donated kidney. Of the 3685 donors, 1211 were estimated to have a remaining kidney with ≥ 2 arteries. Mean follow-up time for the single-artery group was 14.1 (± 11.0) yr and 15.3 (± 11.2) yr for the ≥ 2 artery group. Six-month hospital readmission rate was 1.4% and 1.2%, hypertension was noted in 22.4% and 21.8% and proteinuria in 9.7% and 9.6%, and estimated glomerular filtration rate at last follow-up was 62 (± 28) and 62 (± 16) for single vs. ≥ 2 renal artery groups, respectively. Our data suggest no adverse clinical sequelae nor any decrease in long-term survival for donors left with a kidney having ≥ 2 renal arteries.


Subject(s)
Kidney/physiopathology , Living Donors , Nephrectomy/adverse effects , Nephrectomy/mortality , Postoperative Complications , Renal Artery/physiology , Adult , Creatinine/blood , Female , Follow-Up Studies , Glomerular Filtration Rate , Humans , Hypertension/etiology , Kidney/blood supply , Kidney Function Tests , Male , Prognosis , Proteinuria/etiology , Renal Artery/abnormalities , Renal Insufficiency/etiology , Survival Rate
8.
Transplantation ; 92(1): 70-5, 2011 Jul 15.
Article in English | MEDLINE | ID: mdl-21659945

ABSTRACT

BACKGROUND: Defining living donor (LD)-related risk factors affecting kidney transplant outcome will allow better donor selection and more educated informed consent when there is more than one potential donor. We studied risk factors in a large cohort at a single institution. METHODS: We reviewed 1632 recipients who underwent LD kidney transplantation at the University of Minnesota between January 1, 1990, and October 1, 2009. Using Cox regression, we studied the effect of donor and recipient risk factors on patient and graft survival. We specifically examined the effect of donor age and human leukocyte antigen (HLA) matching because these are variables that may help clinical decision making when multiple potential donors exist. RESULTS: Mean donor age was 40.6 years for all transplants; 180 (11%) donors were 55 years or older, and 24 (1.5%) donors were older than 65 years. Mean number of HLA mismatches (per transplant) was 2.9 (29.2% of recipients had one to two HLA mismatches, 39.8% had three to four HLA mismatches, and 25% had five to six HLA mismatches). Donor age more than 65 years, five to six HLA mismatches, delayed graft function, and acute rejection were independent predictors of decreased patient and graft survival. When controlling for recipient age, donor age more than 65 years remained a risk factor for worse outcome. CONCLUSIONS: Our data suggest that advanced donor age (>65 years) and degree of HLA mismatch (≥5) are independent donor-related risk factors associated with worse outcome. When multiple potential LDs exist, it may be ideal to attempt to use a donor younger than 65 years and with less than five HLA mismatches.


Subject(s)
Donor Selection/methods , Histocompatibility Testing , Kidney Transplantation , Living Donors , Age Factors , Aged , Cohort Studies , Delayed Graft Function/etiology , Delayed Graft Function/immunology , Female , Follow-Up Studies , Graft Rejection/etiology , Graft Rejection/immunology , Humans , Kaplan-Meier Estimate , Kidney Transplantation/adverse effects , Kidney Transplantation/immunology , Male , Middle Aged , Multivariate Analysis , Risk Factors , Treatment Outcome
9.
Transplantation ; 91(12): 1386-91, 2011 Jun 27.
Article in English | MEDLINE | ID: mdl-21508898

ABSTRACT

BACKGROUND: Recurrent glomerulonephritis (GN) remains an important cause of kidney allograft loss and whether rapid discontinuation of steroids (RDS) is associated with a higher risk of recurrence is not known. METHODS: We studied recurrence rate, and graft and patient survival in four groups of recipients: 216 recipients with GN transplanted under RDS (group 1), 978 concurrent non-GN recipients transplanted under RDS (group 2), 260 historic comparator group transplanted for GN between 1994 and 1999 with steroid maintenance (group 3), and 950 recipients who were also transplanted between 1994 and 1999 for non-GN and also maintained on steroids (group 4). Regression analysis adjusting for donor and recipient factors, steroid and sirolimus use, and also GN type was used to address factors associated with recurrent disease. RESULTS: The 1-, 5-, and 7-year recurrence rate in the GN group under RDS was 6.7%, 13.7%, and 19.2% and in historic GN recipients maintained on steroids it was 2.4%, 3.8%, and 5.3%, respectively (P<0.0001). RDS was associated with a higher adjusted risk of recurrent disease for all GN types (hazard ratio 4.86; 95% confidence interval 2.34-10.07; P<0.0001). Graft and patient survival were similar in the two GN groups and both were highest among all groups. Notably, death-censored graft survival was not different among the groups. CONCLUSION: Steroid avoidance may be associated with a higher rate of recurrent GN but no apparent increase in risk of graft loss. This group of recipients needs to be studied more carefully, in larger numbers, and for a longer time period.


Subject(s)
Glomerulonephritis/etiology , Renal Insufficiency/diagnosis , Adult , Female , Glomerulonephritis/mortality , Graft Rejection , Graft Survival , Humans , Immunosuppressive Agents/therapeutic use , Kidney Transplantation/methods , Living Donors , Male , Middle Aged , Recurrence , Renal Insufficiency/mortality , Renal Insufficiency/therapy , Risk , Steroids/therapeutic use , Treatment Outcome
10.
Transplantation ; 88(2): 237-41, 2009 Jul 27.
Article in English | MEDLINE | ID: mdl-19623020

ABSTRACT

BACKGROUND: There are few prospective studies of prednisone-free immunosuppression (IS) in pediatric kidney transplant (KTx) recipients. We studied the outcomes of a protocol using rapid discontinuation of prednisone (RDP, <1 week) and thymoglobulin induction. METHODS: Twenty-one RDP recipients (mean age 14+/-3 years) received KTx between May 2002 and December 2005 and were matched with controls (n=39) for age, race, and donor source. For the RDP group, IS consisted of prednisone tapered off over 6 days, thymoglobulin, mycophenolate mofetil, and cyclosporine A (CsA). In controls, IS consisted of thymoglobulin, maintenance prednisone, azathioprine, and CsA. RESULTS: For the RDP group, graft survival at 1 and 2 years was 90% and 86%; for the controls, graft survival at 1 and 2 years was 92%, and 90% (P=0.86). For the RDP group, the incidence of acute rejection at 1 and 2 years was 14% and 19%; for controls, the incidence of acute rejection at 1 and 2 years was 23%, and 31% (P=0.17). Of the 18 RDP recipients with functioning grafts, 89% remain prednisone-free at follow-up. There was no significant difference between groups in recipient survival rates, incidence of hypertension, chronic allograft nephropathy, or cytomegalovirus disease. CONCLUSIONS: RDP using thymoglobulin, mycophenolate mofetil, and CsA in selected pediatric KTx recipients is associated with recipient and graft survival rates and acute rejection incidence comparable with quadruple drug therapy.


Subject(s)
Immunosuppressive Agents/therapeutic use , Kidney Transplantation/immunology , Prednisone/therapeutic use , Adolescent , Antilymphocyte Serum/therapeutic use , Child , Child, Preschool , Cyclosporine/therapeutic use , Drug Administration Schedule , Drug Therapy, Combination , Glucocorticoids/administration & dosage , Glucocorticoids/therapeutic use , Graft Rejection/epidemiology , Graft Survival/physiology , Humans , Mycophenolic Acid/analogs & derivatives , Mycophenolic Acid/therapeutic use , Prednisone/administration & dosage , Prednisone/adverse effects , Prospective Studies
11.
Transplantation ; 87(1): 100-2, 2009 Jan 15.
Article in English | MEDLINE | ID: mdl-19136898

ABSTRACT

Protocols incorporating rapid discontinuation of prednisone (RDP) after kidney transplantation have been associated with good short-term results. However, concern remains that RDP will be associated with decreased long-term graft survival rates. We compared kidney transplant half-life (t1/2) for recipients treated with antibody induction, calcineurin inhibitor, antimetabolite, and RDP versus historical controls treated with antibody induction, calcineurin inhibitor, antimetabolite, and maintenance prednisone. For both living and deceased donor recipients, we found no difference between groups. We also found no differences in rate of graft loss to acute rejection or to tubular atrophy and interstitial fibrosis. Our study suggests that long-term graft outcome is not decreased when using RDP protocols versus chronic maintenance prednisone.


Subject(s)
Graft Rejection , Graft Survival/drug effects , Kidney Transplantation , Prednisone/pharmacology , Adult , Female , Follow-Up Studies , Humans , Male , Middle Aged , Time Factors
12.
Transplantation ; 85(3): 338-43, 2008 Feb 15.
Article in English | MEDLINE | ID: mdl-18301329

ABSTRACT

BACKGROUND: The benefits (e.g., low acute rejection [AR] rate) vs. the long-term risk of each immunosuppressive protocol may determine the protocol's value. METHODS: We studied the long-term impact of new-onset posttransplant diabetes (PTDM) and/or AR in 1,487 adult, primary transplant, nondiabetic recipients. Per Cox regression, donor source, AR, and PTDM were independent risk factors for graft loss (each, p<.0001). Recipients were subdivided by donor source and into these 4 groups: no AR, no PTDM [n=857]; no AR, PTDM [n=134]; > or =1 AR, no PTDM [n=403]; > or =1 AR, PTDM [n=93]. RESULTS: There was a significant difference between groups in 15-yr actuarial graft survival (GS) and death-censored (DC) GS (p<.0001). Importantly, > or =1 AR had more impact on 15-yr GS and DC GS than did PTDM; the worst outcome was for those having both AR and PTDM. In separate analyses, we censored those with >1 AR; and then only compared those developing AR or PTDM in the first year. The results were similar--the AR (no PTDM) group did worse than the PTDM (no AR) group (p<.001). CONCLUSIONS: Determining long-term risks associated with immunosuppressive protocols is important for treating future patients. Our data suggests that 15-year actuarial outcome (GS and DC GS) is worse for those developing AR than for those developing PTDM.


Subject(s)
Diabetes Mellitus/immunology , Diabetes Mellitus/surgery , Graft Rejection/immunology , Kidney Transplantation/immunology , Acute Disease , Adult , Diabetes Mellitus/drug therapy , Diabetes Mellitus/epidemiology , Female , Humans , Insulin/therapeutic use , Kidney Transplantation/statistics & numerical data , Male , Middle Aged , Recurrence , Time Factors , Treatment Outcome
13.
Transplantation ; 83(6): 722-6, 2007 Mar 27.
Article in English | MEDLINE | ID: mdl-17414704

ABSTRACT

BACKGROUND: Calcineurin inhibitors (CNIs) have been the mainstay of immunosuppressive protocols in kidney transplantation over the past 20 years. However, in some recipients, the adverse effects of CNIs contribute to chronic allograft nephropathy and death with function--the two leading causes of late graft loss. Other recipients maintain stable graft function. METHODS: We studied the impact of continuing CNI-based immunosuppression in the second decade after kidney transplantation. From 1984 through 1996, a total of 1,263 patients underwent a primary kidney transplant at the University of Minnesota and received cyclosporine-based immunosuppression. Antibody induction was used only in deceased donor recipients. RESULTS: The actuarial 20-year patient survival rate was 38%; graft survival, 30%; and death-censored graft survival, 60%. The annual mean serum creatinine level for recipients whose grafts survived > or =1 year remained stable, although recipients with a history of > or =1 acute rejection episode had a higher serum creatinine level vs. recipients who were rejection-free. The annual mean calculated creatinine clearance was also stable over time. In addition, for recipients who were acute rejection-free, chronic allograft nephropathy/chronic rejection was only responsible for 9% of graft losses. CONCLUSIONS: Our study suggests that some kidney transplant recipients tolerate long-term CNI-based immunosuppression with stable creatinine levels. Identifying certain recipients' predisposition to CNI toxicity and individualizing immunosuppressive therapy may be important in order to improve long-term kidney function, while simultaneously preserving low short-term acute rejection rates.


Subject(s)
Cyclosporine/therapeutic use , Immunosuppressive Agents/therapeutic use , Kidney Transplantation/physiology , Kidney/physiology , Adult , Calcineurin Inhibitors , Creatinine/blood , Cyclosporine/adverse effects , Graft Rejection/chemically induced , Humans , Kidney Transplantation/methods , Logistic Models , Longitudinal Studies , Middle Aged , Retrospective Studies
14.
Clin Transplant ; 20(6): 667-72, 2006.
Article in English | MEDLINE | ID: mdl-17100713

ABSTRACT

BACKGROUND: Determining factors associated with negative slope of inverse creatinine vs. time (1/Cr vs. t) may help prevent a decline in renal allograft function. METHODS: A total of 1389 adult recipients of primary renal transplants were divided into quartiles based on the slope of 1/Cr vs. t calculated from 6 and 12 months post transplant. A multivariate analysis of risk factors for being in the worst vs. best quartile employed these variables: donor source, HLA mismatch, recipient age, donor age, panel-reactive antibody (PRA), acute rejection (AR), 3-month cyclosporin A (CsA) level, 1-yr CsA level and acute tubular necrosis. Two separate analyses compared risk factors in patients with 1 and 3 yr survival, respectively. RESULTS: In recipients with > or = 1 yr graft survival, high PRA and AR were associated with negative slopes of 1/Cr vs. t. For those with > or = 3 yr graft survival, both AR and 3-month CsA level > 150 ng/mL were significant risk factors, using both 6- and 12-month slopes. Stratification of AR showed 1 AR episode > or = 6 months and multiple AR episodes carried significant risk for negative slopes. CONCLUSION: Optimization of allograft function invokes a conundrum between the needs to avoid both AR and high early CsA levels. We support a policy of carefully balancing these two risks.


Subject(s)
Creatinine/blood , Graft Rejection/blood , Graft Survival/physiology , Kidney Failure, Chronic/blood , Kidney Transplantation , Adult , Biomarkers/blood , Female , Follow-Up Studies , Graft Rejection/complications , Humans , Kidney Failure, Chronic/etiology , Male , Prognosis , Retrospective Studies , Risk Factors , Time Factors , Transplantation, Homologous
15.
Transplantation ; 81(2): 214-9, 2006 Jan 27.
Article in English | MEDLINE | ID: mdl-16436965

ABSTRACT

BACKGROUND: The risk of recurrence of glomerulonephritis in kidney transplant recipients on a steroid-free maintenance immunosuppression protocol is unknown. METHODS: We studied the 4-year graft and patient survival in 105 adult kidney transplant recipients who received their transplant for glomerulonephritis (GN) and were treated with a protocol incorporating rapid discontinuation of prednisone for 5 days (group 1). We compared these outcomes to two control groups; 439 concurrent recipients who received a transplant for causes other than GN (group 2) and to 260 kidney transplant recipients who received an allograft for GN between 1994 and 1999 and were maintained on a steroid-based immunosuppressive protocol (group 3). RESULTS: The 4-year graft and patient survival were similar in the three groups. Acute rejection-free survival was also similar. Serial annual serum creatinine and estimated GFR were also comparable amongst the three groups. Two grafts were lost in group 1 from biopsy-proven recurrent GN and eight other subjects had evidence of histological recurrence at 11.2+/-11.9 months. Seven grafts were lost for recurrent disease in group 3 and 15 others had evidence of histological recurrence at 29.1+/-32.6 months. The mean time to graft loss from recurrence was 52+/-22 months. CONCLUSION: A regimen that utilizes rapid discontinuation of steroids conveys no added risk of graft loss from recurrent GN in the short term but longer follow-up is needed. A consideration should be made to discontinue corticosteroids in the potential recipients who are on them at the time of transplantation.


Subject(s)
Glomerulonephritis/complications , Glomerulonephritis/surgery , Graft Rejection/etiology , Immunosuppressive Agents/administration & dosage , Kidney Transplantation/adverse effects , Steroids/administration & dosage , Adolescent , Adult , Aged , Clinical Protocols , Creatinine/blood , Female , Glomerulonephritis/blood , Glomerulonephritis/mortality , Graft Rejection/blood , Graft Survival , Humans , Kidney Transplantation/mortality , Male , Middle Aged , Recurrence , Survival Rate
16.
Am J Transplant ; 5(10): 2473-8, 2005 Oct.
Article in English | MEDLINE | ID: mdl-16162197

ABSTRACT

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.


Subject(s)
Immunosuppressive Agents/therapeutic use , Kidney Transplantation/methods , Prednisone/administration & dosage , Anti-Infective Agents/therapeutic use , Antifungal Agents/therapeutic use , Antiviral Agents/therapeutic use , Cataract/etiology , Clotrimazole/therapeutic use , Cohort Studies , Creatinine/blood , Dapsone/therapeutic use , Diabetes Mellitus/etiology , Fractures, Bone/etiology , Ganciclovir/analogs & derivatives , Ganciclovir/therapeutic use , Graft Rejection , Graft Survival , Humans , Immunosuppression Therapy , Immunosuppressive Agents/administration & dosage , Necrosis/etiology , Nystatin/therapeutic use , Pentamidine/therapeutic use , Time Factors , Transplantation, Homologous/methods , Treatment Outcome , Trimethoprim, Sulfamethoxazole Drug Combination/therapeutic use , Valganciclovir
17.
Am J Transplant ; 5(6): 1529-36, 2005 Jun.
Article in English | MEDLINE | ID: mdl-15888064

ABSTRACT

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.


Subject(s)
Graft Rejection/prevention & control , Graft Survival , Immunosuppressive Agents/therapeutic use , Kidney Transplantation , Antilymphocyte Serum/therapeutic use , Cyclosporine/therapeutic use , Drug Therapy, Combination , Humans , Living Donors , Middle Aged , Mycophenolic Acid/analogs & derivatives , Mycophenolic Acid/therapeutic use , Pancreas Transplantation/immunology , Prospective Studies , Sirolimus/therapeutic use , Tacrolimus/therapeutic use , Treatment Outcome
18.
Transplantation ; 79(8): 958-63, 2005 Apr 27.
Article in English | MEDLINE | ID: mdl-15849550

ABSTRACT

BACKGROUND: Induction immunosuppressive therapy with the anti-T-cell antibody Thymoglobulin decreases the incidence of acute rejection in adult kidney transplant (KTx) recipients, but limited data are available for pediatric KTx recipients. METHODS: We conducted a historical cohort study to compare rates of survival, rejection, and infection in pediatric (age <19 years) KTx recipients who received induction therapy with polyclonal antibody, ATGAM (n=127) or Thymoglobulin (n=71), from December 1, 1992, to January 31, 2003. Maintenance immunosuppression included cyclosporine, azathioprine or mycophenolate mofetil, and prednisone. Mean follow-up was 90+/-25 months for ATGAM recipients and 32+/-15 months for Thymoglobulin recipients. RESULTS: Overall, the incidence of acute rejection was lower in Thymoglobulin recipients versus ATGAM recipients (33% vs. 50%, P=0.02). Epstein-Barr virus (EBV) infection was higher in Thymoglobulin recipients versus ATGAM recipients (8% vs. 3%, P=0.002). But the two groups did not significantly differ in patient and graft survival rates, incidence of chronic rejection, EBV lymphoma, or other infection. CONCLUSIONS: Thus, Thymoglobulin induction was associated with a decreased incidence of acute rejection and an increased incidence of EBV infection in pediatric KTx recipients. EBV monitoring should be performed in EBV-naive recipients receiving Thymoglobulin.


Subject(s)
Antilymphocyte Serum/pharmacology , Immunotherapy/methods , Kidney Transplantation/immunology , T-Lymphocytes/immunology , Adolescent , Antilymphocyte Serum/immunology , Child , Child, Preschool , Female , Follow-Up Studies , Graft Rejection/immunology , Graft Survival/drug effects , Graft Survival/immunology , Humans , Infant , Infections/complications , Male , Survival Rate , Treatment Outcome
19.
Transplantation ; 78(9): 1319-23, 2004 Nov 15.
Article in English | MEDLINE | ID: mdl-15548970

ABSTRACT

BACKGROUND: Urolithiasis occurs in approximately 6% of adult kidney transplant (KTx) recipients. Limited data are available on urolithiasis after pediatric KTx. We report the incidence, management of, and risk factors for stone development in children after KTx. METHODS: We reviewed the medical records of 399 children who received KTx at our center between September 1986 and January 2003. Transplant outcomes were compared in stone formers and controls. RESULTS: Twenty (5%) patients, age 9+/-5 (X +/- SD) years, developed stones over the follow-up period (74+/-53 months). Time to stone presentation was 19+/-22 months post-KTx. Presenting features were urinary tract infection (UTI), 8; gross hematuria, 5; microscopic hematuria, 2; dysuria without infection, 6; difficulty voiding, 3; and silent stones, 2. Stones were removed by cystoscopy in 11 (55%) patients. Stone composition was determined in 11 patients: calcium phosphate (55%), calcium oxalate (18%), mixed calcium phosphate and oxalate (9%), and struvite (18%). Factors predisposing to stones in study patients included suture retention (n = 4), elevated urinary calcium excretion (n = 2), recurrent UTI (n = 2), and urinary stasis (n = 2). The incidence of UTI was higher (P = 0.003) and of acute rejection was lower (P = 0.02) in stone patients compared with controls. Patient and graft survival rates and the incidence of chronic rejection did not significantly differ between study patients and controls (P = NS). CONCLUSIONS: Urolithiasis is not uncommon in pediatric KTx patients. Factors associated with post-KTx urolithiasis include retention of suture material, recurrent UTI, hypercalciuria, and urinary stasis. Treatment is associated with excellent outcome and low recurrence rate.


Subject(s)
Kidney Transplantation/adverse effects , Urinary Calculi/etiology , Adolescent , Calcium/urine , Child , Child, Preschool , Female , Humans , Infant , Male , Risk Factors , Urinary Tract Infections/complications
20.
Transplantation ; 78(9): 1397-9, 2004 Nov 15.
Article in English | MEDLINE | ID: mdl-15548981

ABSTRACT

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.


Subject(s)
Immunosuppression Therapy , Kidney Transplantation , Prednisone/administration & dosage , Humans , Kidney Transplantation/immunology , Kidney Transplantation/mortality , Risk , Survival Rate
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