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Kidney Recipients (kidney + recipient)

Distribution by Scientific Domains

Medical Sciences	100%

Kinds of Kidney Recipients

pediatric kidney recipient

Selected Abstracts

Impaired Insulin Sensitivity as an Underlying Mechanism Linking Hepatitis C and Posttransplant Diabetes Mellitus in Kidney Recipients

AMERICAN JOURNAL OF TRANSPLANTATION, Issue 12 2009
S. Baid-Agrawal
Aim of this study was to investigate the mechanism/s associating hepatitis C virus (HCV) infection and posttransplant diabetes mellitus in kidney recipients. Twenty HCV-positive and 22 HCV-negative kidney recipients, 14 HCV-positive nontransplant patients and 24 HCV-negative nontransplant (healthy) subjects were analyzed. A 3-h intravenous glucose tolerance test was performed; peripheral insulin sensitivity was assessed by minimal modeling. Pancreatic insulin secretion, hepatic insulin uptake, pancreatic antibodies and proinflammatory cytokines in serum (tumor necrosis factor-,, intereukin-6, high-sensitive C-reactive protein) were also assessed. HCV-positive recipients showed a significantly lower insulin sensitivity as compared to HCV-negative recipients (3.0 ± 2.1 vs. 4.9 ± 3.0 min,1.,U.mL, 1.104, p = 0.02), however, insulin secretion and hepatic insulin uptake were not significantly different. Pancreatic antibodies were negative in all. HCV status was an independent predictor of impaired insulin sensitivity (multivariate analysis, p = 0.008). The decrease of insulin sensitivity due to HCV was comparable for transplant and non-transplant subjects. No significant correlation was found between any of the cytokines and insulin sensitivity. Our results suggest that impaired peripheral insulin sensitivity is associated with HCV infection irrespective of the transplant status, and is the most likely pathogenic mechanism involved in the development of type 2 diabetes mellitus associated with HCV infection. [source]

Maintenance Steroid Therapy for Kidney Recipients,Not Ready for Relegation

AMERICAN JOURNAL OF TRANSPLANTATION, Issue 6 2009
N. M. Desai
The recent report of the first randomized, double-blind, controlled trial of steroid withdrawal in kidney transplant recipients demonstrated equivalent patient and graft survival, but rejection and fibrosis were increased in the steroid-free recipients. [source]

Prospective Monitoring of Polyomavirus BK Replication and Impact of Pre-Emptive Intervention in Pediatric Kidney Recipients

AMERICAN JOURNAL OF TRANSPLANTATION, Issue 12 2007
F. Ginevri
Polyoma BK virus (BKV)-associated nephropathy (PVAN) is a relevant cause of poor renal allograft survival. In a prospective analysis, we monitored BKV DNA in blood and urine samples from 62 consecutive pediatric kidney recipients. In patients with BKV replication, we analyzed the impact of reduction of maintenance immunosuppression on viral load kinetics and PVAN in patients with BKV replication. BKV-specific immunity was concomitantly evaluated on blood samples of viremic patients, by measuring the frequency of BKV-specific interferon-,-producing and cytotoxic T cells, and BKV IgG antibody levels. At a median follow-up of 24 months, BK viruria was observed in 39 of 62 patients, while BK viremia developed in 13 patients (21%). In all viremic patients, immunosuppression reduction resulted in the clearance of viremia, and prevented development of PVAN, without increasing the rate of acute rejection or causing graft dysfunction. As a consequence of immunosuppression adjustment, an expansion of BKV-specific cellular immunity was observed that coincided with viral clearance. We conclude that treating pediatric kidney transplant patients pre-emptively with immunosuppression reduction guided by BKV DNA in blood is safe and effective to prevent onset of PVAN. BKV-specific cellular immunity may be useful to guide this intervention. [source]

Laparoscopic Live Donor Nephrectomy: A Risk Factor for Delayed Function and Rejection in Pediatric Kidney Recipients?

AMERICAN JOURNAL OF TRANSPLANTATION, Issue 1 2005
A UNOS Analysis
The impact of laparoscopic (vs. open) donor nephrectomy on early graft function and survival in pediatric kidney recipients (,18 years) is unknown. We studied 995 pediatric live donor txs reported to UNOS from January 2000 to June 2002, in two recipient age groups: 0,5 years (n = 212, 44% laparoscopic donors [LapD]) and 6,18 years (n = 783, 50% LapD). Delayed graft function (DGF) rates were higher for LapD versus open donor (OpD) txs (0,5 years, 12.8% vs. 2.5%[p = 0.004]; 6,18 years, 5.9% vs. 2.8%[p = 0.03]). Acute rejection incidence for LapD versus OpD txs was higher at 6 months for recipients 0,5 years (18.6% vs. 5.9%, p = 0.01) and 6,18 years (22.5% vs. 15.6%, p = 0.03), and 1 year for recipients 0,5 years (24.3% vs. 7.9%, p = 0.004). In multivariate analyses, significant independent risk factors for rejection at 6 months and 1 year were recipient age 6,18 years, pretx dialysis, LapD nephrectomy and DGF. Graft survival was similar for LapD versus OpD txs. In this retrospective UNOS database analysis, LapD procurement was associated with increased DGF and an independent risk factor for rejection during the first year, particularly for recipients 0,5-years old. Future investigations must confirm these findings and identify strategies to optimize procurement and pediatric recipient outcome. [source]

Incidence Rate and Outcome of Gram-Negative Bloodstream Infection in Solid Organ Transplant Recipients

AMERICAN JOURNAL OF TRANSPLANTATION, Issue 4 2009
M. N. Al-Hasan
Bacterial infections are common complications of solid organ transplantation (SOT). In this study, we defined the incidence, mortality and in vitro antimicrobial resistance rates of Gram-negative bloodstream infection (BSI) in SOT recipients. We identified 223 patients who developed Gram-negative BSI among a cohort of 3367 SOT recipients who were prospectively followed at the Mayo Clinic (Rochester, MN) from January 1, 1996 to December 31, 2007. The highest incidence rate (IR) of Gram-negative BSI was observed within the first month following SOT (210.3/1000 person-years [95% confidence interval (CI): 159.3,268.3]), with a sharp decline to 25.7 (95% CI: 20.1,32.1) and 8.2 (95% CI: 6.7,10.0) per 1000 person-years between 2 and 12 months and more than 12 months following SOT, respectively. Kidney recipients were more likely to develop Gram-negative BSI after 12 months following transplantation than were liver recipients (10.3 [95% CI: 7.9,13.1] vs. 5.2 [95% CI: 3.1,7.8] per 1000 person-years). The overall unadjusted 28-day all-cause mortality of Gram-negative BSI was 4.9% and was lower in kidney than in liver recipients (1.6% vs. 13.2%, p < 0.001). We observed a linear trend of increasing resistance among Escherichia coli isolates to fluoroquinolone antibiotics from 0% to 44% (p = 0.002) throughout the study period. This increase in antimicrobial resistance may influence the choice of empiric therapy. [source]

Angiotensinogen and plasminogen activator inhibitor-1 gene polymorphism in relation to chronic allograft dysfunction,

CLINICAL TRANSPLANTATION, Issue 1 2005
Kadriye Reis
Abstract:, Chronic allograft dysfunction (CAD) is the most common cause of allograft failure in the long-term, and current immunologic strategies have little effect on this condition. The renin-angiotensin system (RAS) plays important roles progression of chronic renal disease. It is thought that plasminogen activator inhibitor-1 (PAI-1) functions in the RAS, in addition to involvement in thrombotic risk and fibrosis. This study investigated possible links between angiotensinogen (AGT) genotypes (M235T/MM, MT, TT) and PAI-1 genotypes (4G4G, 4G5G, 5G5G) and CAD assessments of both types of polymorphism were performed in 82 renal allograft recipients. One hundred healthy subjects were also investigated for AGT polymorphism, and 80 healthy subjects for PAI-1 polymorphism. Genotypes were determined using polymerase chain reaction (PCR) sequence-specific primers, and PCR followed by restriction fragment length polymorphism analysis. Kidney recipients with CAD had significantly lower frequencies of the MM genotype and the M allele than the recipients without CAD (p < 0.05 and <0.001). The transplant recipients with CAD also had significantly lower frequencies of the 5G5G genotype and the 5G allele than those without CAD (p < 0.001 and <0.05). Determination of AGT M235T and PAI-1 genotypes prior to transplantation may help identify patients who at risk for chronic renal transplant dysfunction. [source]

Postrenal Transplant Hemophagocytic Lymphohistiocytosis and Thrombotic Microangiopathy Associated with Parvovirus B19 Infection

AMERICAN JOURNAL OF TRANSPLANTATION, Issue 6 2008
M. R. Ardalan
Persistent anemia is a known consequence of Parvovirus B19 (B19) infection following renal transplantation. However, to date, no description of B19-related hemophagocytic lymphohistiocytosis (HLH) exists in renal transplant recipients. We report a 24-year-old male kidney recipient, who presented with fever, severe anemia and allograft dysfunction two years following transplantation. Hyperferritinemia, hypertriglyceridemia, elevated serum lactate dehydrogenase, pancytopenia and fragmented red blood cells on the peripheral blood were also noted. Bone marrow examination revealed giant pronormoblasts and frequent histiocytes with intracellular hematopoietic elements, consistent with HLH. Renal allograft biopsy revealed closure of the lumen of glomerular capillaries and thickening of the capillary walls compatible with thrombotic microangiopathy. The presence of anti-B19 IgM antibody and viral DNA in the patient's serum (detected by real-time PCR) confirmed an acute B19 infection. Following high-dose intravenous immunoglobulin therapy, the anemia gradually resolved and renal function improved. As far as we know, this is the first report of B19-associated HLH and thrombotic microangiopathy in a renal transplant recipient. [source]

Experience of Hong Kong patients awaiting kidney transplantation in mainland China

JOURNAL OF CLINICAL NURSING, Issue 11c 2007
Sylvie SH Leung MN
Aim., This paper describes the experience of Hong Kong Chinese patients awaiting kidney transplantation in mainland China. Background., While travelling to mainland China for kidney transplantation is a controversial issue, there is an increasing trend of Hong Kong Chinese patients with chronic kidney disease seeking this treatment choice, which outnumbers that performed in Hong Kong. Although these patients seek pre- and post-transplantation care from Hong Kong public healthcare system, little is known about their experience during the waiting period. Methods., This experience is examined in an exploratory qualitative study. In-depth interviews were used to collect data from a purposive sample of 12 kidney recipients. Results., Three major findings are identified: (i) transplant waiting patients may travel to mainland China for transplantation in search of normal life, (ii) they need informational support from their continuing healthcare providers in Hong Kong to make the informed decision and (iii) they perceive a variation of attitudes of nurses and doctors in Hong Kong towards transplantation in mainland China. Conclusions., This study contributes to the literature by researching patients' perspective. The findings highlight the importance and controversy of addressing these patients' informational needs. While the authors have no inclination for or against travelling to mainland China for transplantation, the findings reveal a tenacious clinical dilemma, which deserves debate in international transplant community and further research to inform the debate. Nurse and doctors in Hong Kong may contribute to the debate by articulating their experience of caring for these patients. Relevance to clinical practice., Health information that is readily available for patients scheduled for kidney transplantation in Hong Kong should be made accessible to the whole community of patients with chronic kidney disease. To address the complexity of patients travelling to elsewhere for transplantation and the needs of these patients, provider reticence may be counterproductive. [source]

Transmission of an undiagnosed sarcoma to recipients of kidney and liver grafts procured in a non-heart beating donor

LIVER TRANSPLANTATION, Issue 6 2005
Olivier Detry
Transmission of an undiagnosed cancer with solid organ transplantation is a rare but dreadful event. In this paper the authors report the transmission of an undiagnosed sarcoma to recipients of kidney and liver grafts procured in a Maastricht category 3 non-heart beating donor. To the authors' knowledge this case is the first report of such a transmission with a liver graft procured in a non-heart beating donor. The cancer transferal was diagnosed 1 year after transplantation in the recipients of the liver and of one kidney. The liver recipient died from multiple organ failure after a failed attempt of tumor resection. The kidney recipient underwent immunosuppression withdrawal and transplantectomy. Non-heart beating donors should not be particularly at risk for undiagnosed cancer transmission if the procurement is performed according to the same rules of careful inspection of the abdominal and thoracic organs. After diagnosis of donor cancer transmission, kidney recipients should have the graft removed, and immunosuppression should be interrupted. The management of liver graft recipients is very difficult in this setting, and long-term survival was very rarely reported. (Liver Transpl 2005;11:696,699.) [source]

Post-transplant glucose status in 61 pediatric renal transplant recipients: Preliminary results of five Turkish pediatric nephrology centers

PEDIATRIC TRANSPLANTATION, Issue 2 2010
Necla Buyan
Buyan N, Bilge I, Turkmen MA, Bayrakci U, Emre S, Fidan K, Baskin E, Gok F, Bas F, Bideci A. Post-transplant glucose status in 61 pediatric renal transplant recipients: Preliminary results of five Turkish pediatric nephrology centers. Pediatr Transplantation 2010:14:203,211 © 2009 John Wiley & Sons A/S. Abstract:, To assess the incidence, risk factors and outcomes of PTDM, a total of 61 non-diabetic children (24 girls, 37 boys, age: 14.5 ± 2.1 yr) were examined after their first kidney transplantation (37.3 ± 21.6 months) with an OGTT. At baseline, 16 (26.2%) patients had IGT, 45 (73.8%) had NGT, and no patient had PTDM. No significant difference was shown between TAC- and CSA-treated patients in terms of IGT. Higher BMI z -scores (p = 0.011), LDL-cholesterol (p < 0.05) and triglyceride levels (p < 0.01), HOMA-IR (p = 0.013) and lower HOMA-%, (p = 0.011) were significantly associated with IGT. Fifty-four patients were re-evaluated after six months; eight patients with baseline IGT (50%) improved to NGT, three (19%) developed PTDM requiring insulin therapy, five (31%) remained with IGT, and four patients progressed from NGT to either IGT (two) or PTDM (two). These 12 progressive patients had significantly higher total cholesterol (p < 0.05), triglycerides (p < 0.05), HOMA-IR (p < 0.01) and lower HOMA-%, (p < 0.0) than non-progressive patients at baseline. We can conclude that post-transplantation glucose abnormalities are common in Turkish pediatric kidney recipients, and higher BMI z -scores and triglyceride concentrations are the main risk factors. Considering that the progressive patients are significantly more insulin resistant at baseline, we suggest that the utility of both HOMA-IR and HOMA-%, in predicting future risk of PTDM and/or IGT should be evaluated in children. [source]

Limited surgical interventions in children with posterior urethral valves can lead to better outcomes following renal transplantation

PEDIATRIC TRANSPLANTATION, Issue 5 2002
Leah Bartsch
Abstract: There is currently no consensus as to the most appropriate means by which children with posterior urethral valves (PUV) are to be managed prior to transplantation. We compared (i) renal allograft survival and function in patients with PUV vs. those with non-obstructive causes of ESRD and (ii) graft outcomes in children who had limited interventions (Group 1) vs. those with more extensive urologic surgeries to decompress the urinary tract (Group 2). Twenty-six pediatric renal transplant recipients had ESRD due to PUV (Group 1, n = 16; Group 2, n = 10). The study group was compared to 23 matched controls with ESRD due to non-obstructive causes. Five yr patient and graft survival was similar in all patients with PUV (Groups 1 and 2) when compared to all other kidney recipients in the transplant program, 96.2% vs. 98.0% and 87.5% vs. 87.0%, respectively. Although calculated creatinine clearance (Ccr), was similar between the PUV group and controls for the first 4 yr, the 5 yr graft function was significantly lower in the PUV group. (53.7 ± 15.7 vs. 70.2 ± 21.0 mL/min/1.73 m2; p = 0.03). When the two PUV groups were compared, graft survival was equivalent, but graft function was significantly better at 5 yr in Group 1(60.4 ± 10.8 vs. 33.8 ± 9.3 mL/min/1.73 m2; p = 0.02). Thus, patients with PUV managed by a limited intervention approach of vesicostomy with delayed valve ablation or primary valve ablation, had better outcomes. When ESRD is virtually certain, additional pre-transplant surgeries affecting the urinary tract should be avoided. [source]

Pretransplantation voiding cystography is not necessary for all potential pediatric kidney recipients

PEDIATRIC TRANSPLANTATION, Issue 2 2001
Oscar Salvatierra MD
No abstract is available for this article. [source]

The Quality of Health Insurance Service Delivery for Kidney Transplant Recipients: A Patient Perspective

AMERICAN JOURNAL OF TRANSPLANTATION, Issue 10 2010
E. J. Gordon
Increased attention has been devoted to improving quality care in kidney transplantation. The discourse on quality care has focused on transplant center metrics and other clinical parameters. However, there has been little discussion on the quality of health insurance service delivery, which may be critical to kidney recipients' access to transplantation and immunosuppression. This paper describes and provides a framework for characterizing kidney transplant recipients' positive and negative interactions with their insurers. A consecutive cohort of kidney recipients (n = 87) participated in semistructured interviews on their interactions with insurance agencies. Patients reported negative (37%) and/or neutral or positive (79%) interactions with their insurer (a subset [16%] reported both). Perceived negative experiences included: poor service, logistical difficulties with confusing and time-consuming paperwork, poor communication, rude behavior and concerns about adequate coverage. Positive experiences related to: having good coverage, a simple application process, straightforward transactions and helpful communication. Findings suggest that even when patients have insurance coverage, difficult interactions with insurers and limited skills in navigating insurance options may limit their access to needed medications and health services. Future research is needed to test this hypothesis in a larger population. [source]

Solid Organ Transplantation in AL Amyloidosis

AMERICAN JOURNAL OF TRANSPLANTATION, Issue 9 2010
P. T. Sattianayagam
Vital organ failure remains common in AL amyloidosis. Solid organ transplantation is contentious because of the multisystem nature of this disease and risk of recurrence in the graft. We report outcome among all AL patients evaluated at the UK National Amyloidosis Centre who received solid organ transplants between 1984 and 2009. Renal, cardiac and liver transplants were performed in 22, 14 and 9 patients respectively, representing <2% of all AL patients assessed during the period. One and 5-year patient survival was 95% and 67% among kidney recipients, 86% and 45% among heart recipients and 33% and 22% among liver recipients. No renal graft failed due to recurrent amyloid during median (range) follow up of 4.8 (0.2,13.3) years. Median patient survival was 9.7 years among 8/14 cardiac transplant recipients who underwent subsequent stem cell transplantation (SCT) and 3.4 years in six patients who did not undergo SCT (p = 0.01). Amyloid was widespread in all liver transplant recipients. Solid organ transplantation has rarely been performed in AL amyloidosis, but these findings demonstrate feasibility and support a role in selected patients. [source]

Clinical Predictors of Proteinuria after Conversion to Sirolimus in Kidney Transplant Recipients

AMERICAN JOURNAL OF TRANSPLANTATION, Issue 2 2010
A. Padiyar
Proteinuria is an increasingly recognized effect of sirolimus (SRL) therapy in kidney transplant recipients. Predictors of proteinuria after conversion to SRL are not well described, and in particular the risk in African-American (AA) kidney recipients is unknown. We sought to analyze risk factors for proteinuria with SRL therapy in a cohort of 39 patients (44% AA) converted from tacrolimus to SRL at a mean time of 4 months posttransplantation. Patients were maintained on therapy with mycophenolate mofetil while most patients underwent early steroid withdrawal. Urinary protein to creatinine ratio (Up/cr) at a mean of 14 months postconversion increased to ,500 mg/g in 65% of AAs versus 14% of non-AAs (p = 0.001). Mean arterial blood pressure at the time of conversion and pretransplant proteinuric kidney disease were also predictors of proteinuria after SRL conversion. In conclusion, AAs appear to be at high risk for proteinuria and should be monitored closely after conversion to SRL in calcineurin inhibitor sparing protocols. [source]

The Impact of C4d Pattern and Donor-Specific Antibody on Graft Survival in Recipients Requiring Indication Renal Allograft Biopsy

AMERICAN JOURNAL OF TRANSPLANTATION, Issue 12 2009
A. Haririan
We examined the pattern of PTC C4d by immunohistochemistry and DSA in 297 kidney recipients with indication biopsies, and evaluated their predictive value for graft survival. Median biopsy time was 5.1 months posttransplant. Patients were followed for 17.9 ± 9.4 months postbiopsy. An 18.5% had focal and 15.2% had diffuse C4d, with comparable graft survival (adjusted graft failure HR: 2.3, p = 0.001; HR:1.9, p < 0.02, respectively). 31.3% were DSA+, 19.5% class I and 22.9% class II DSA. Only those with class II DSA had worse outcome (adjusted HR:2.5, p = 0.001 for class II only; HR:2.7, p < 0.001 for class I/II DSA). Among patients with <10%C4d, 23.9% had DSA, compared to 68.9% with diffuse staining. For patients biopsied in first-year posttransplant presence of DSA, regardless of C4d positivity in biopsy, was a poor prognostic factor (adjusted graft failure HR: 4.2, p < 0.02 for C4d,/DSA+; HR:4.9, p = 0.001 for C4d+/DSA+), unlike those biopsied later. We have shown that focal C4d had similar impact on graft survival as diffuse pattern. During the first-year posttransplant either class I or II DSA, and afterward only class II DSA were associated with worse graft survival. DSA was predictive of worse outcome regardless of C4d for patients biopsied in first year and only with C4d positivity afterward, supporting the importance of assessment of both DSA and C4d pattern in biopsy. [source]

Impaired Insulin Sensitivity as an Underlying Mechanism Linking Hepatitis C and Posttransplant Diabetes Mellitus in Kidney Recipients

The Impact of Preexisting or Acquired Kaposi Sarcoma Herpesvirus Infection in Kidney Transplant Recipients on Morbidity and Survival

AMERICAN JOURNAL OF TRANSPLANTATION, Issue 11 2009
C. Francès
The impact of preexisting or acquired Kaposi sarcoma herpesvirus (KSHV) infection in kidney transplant recipients was evaluated in a prospective study. Serum collected from kidney donors and recipients before transplantation were tested for antibodies against KSHV latent nuclear antigen. Three groups of recipients were defined: group A (KSHV+), group B (KSHV,, KSHV+ donor) and group C (donor and recipient KSHV,). Blood was collected from recipients, every 3 months for 3 years, for KSHV viremia (groups A and B), quantitative (group A) and qualitative serology (group B). Data of group C recipients were extracted from a French database. The prevalence of KSHV antibodies was 1.1% in donors and 3.2% in recipients. There were respectively 161, 64 and 4744 recipients in groups A, B and C. In group A, 13% developed Kaposi's sarcoma (KS). Age >53.5 years (p = 0.025) and black skin (p = 0.0054) were associated with KS development. In group B, three recipients developed clinical manifestations related to KSHV infection. There was no difference in terms of survival and graft loss between the three groups. In conclusion, although kidney recipients should be aware of the additional risk of KSHV morbidity, KSHV+ recipients should not be systematically excluded from kidney transplantation. [source]

Transplantation of Kidneys from Donors at Increased Risk for Blood-Borne Viral Infection: Recipient Outcomes and Patterns of Organ Use

AMERICAN JOURNAL OF TRANSPLANTATION, Issue 10 2009
P. P. Reese
Kidney transplantation from deceased donors classified as increased risk for viral infection by the Centers for Disease Control (CDC) is controversial. Analyses of Organ Procurement and Transplantation Network (OPTN) data from 7/1/2004 to 7/1/2006 were performed. The primary cohort included 48 054 adults added to the kidney transplant wait list. Compared to receiving a standard criteria donor (SCD) kidney or remaining wait-listed, CDC recipients (HR 0.80, p = 0.18) had no significant difference in mortality. In a secondary cohort of 19 872 kidney recipients at 180 centers, SCD (reference) and CDC (HR 0.91, p = 0.16) recipients had no difference in the combined endpoint of allograft failure or death. Among centers performing >10 kidney transplants during the study period, the median proportion of CDC transplants/total transplants was 7.2% (range 1.1,35.6%). Higher volume transplant centers were more likely to use CDC kidneys compared to low and intermediate volume centers (p < 0.01). An analysis of procured kidneys revealed that 6.8% of SCD versus 7.8% of CDC (p = 0.13) kidneys were discarded. In summary, center use of CDC kidneys varied widely, and recipients had good short-term outcomes. OPTN should collect detailed data about long-term outcomes and recipient viral testing so the potential risks of CDC kidneys can be fully evaluated. [source]

Fixed- or Controlled-Dose Mycophenolate Mofetil with Standard- or Reduced-Dose Calcineurin Inhibitors: The Opticept Trial

AMERICAN JOURNAL OF TRANSPLANTATION, Issue 7 2009
R. S. Gaston
Mycophenolate mofetil (MMF) was developed with cyclosporine as a fixed-dose immunosuppressant. More recent data indicate a relationship between mycophenolic acid (MPA) exposure in individuals and clinical endpoints of rejection and toxicity. This 2-year, open-label, randomized, multicenter trial compared the efficacy and safety of concentration-controlled MMF (MMFCC) dosing with a fixed-dose regimen in 720 kidney recipients. Patients received either (A) MMFCC and reduced-level calcineurin inhibitor (MMFCC/CNIRL); (B) MMFCC and standard-level CNI (MMFCC/CNISL); or (C) fixed-dose MMF and CNISL (MMFFD/CNISL). Antibody induction and steroid use were according to center practice. The primary endpoint was noninferiority (,= 0.05) of group A versus group C for treatment failure (including biopsy-proven acute rejection [BPAR], graft loss and death) at 1 year. Although mean CNI trough levels in group A did not reach the prespecified targets, they were statistically lower than those in groups B and C (p , 0.01 for each comparison). BPAR rates (8.5%) were low across groups. Group A had 19% fewer treatment failures (23% vs. 28%, p = 0.18). MMF doses were highest (p < 0.05), with withdrawals for adverse events the fewest (p = 0.02), in group A. Of the 80% of subjects taking tacrolimus (Tac), those with higher MPA exposure had significantly less rejection (p < 0.001) and diarrhea correlated with Tac, but not with MPA levels. Thus, MMFCC with low-dose CNI resulted in outcomes not inferior to those with standard CNI exposure and MMFFD, indicating potential utility of MMFCC in CNI-sparing regimens. [source]

Selective Retransplant After Graft Loss to Nonadherence: Success with a Second Chance

AMERICAN JOURNAL OF TRANSPLANTATION, Issue 6 2009
T. B. Dunn
Nonadherence (NA) is a difficult posttransplant problem that can lead to graft loss. A retransplant is controversial because of a fear of recurrent NA. We reviewed our center's data base and identified 114 kidney recipients who lost their graft to overt NA; of this group, 35 (31%) underwent a retransplant after a thorough reevaluation. We compared this NA retransplant group to a control group of second transplant recipients who did not lose their first graft to overt NA (non-NA) (n = 552). After 8 years of follow-up, we found no significant differences between the groups in actuarial graft or patient survival rates, renal function, or the incidence of biopsy-proven chronic rejection. However, 5 of 35 (14%) NA recipients versus 10 of 552 (2%) non-NA recipients lost their retransplant to NA (p = 0.0001). Twenty of 35 (57%) of the NA group exhibited repeat NA behavior after retransplant. We conclude that prior graft loss to NA is associated with increased graft loss to NA after retransplant. However, the majority of NA retransplant recipients did well,with overall long-term outcomes similar to those of the non-NA group. With careful patient selection and aggressive intervention, prior overt NA should not be an absolute contraindication to retransplantation. [source]

Steroid-Free Immunosuppression Since 1999: 129 Pediatric Renal Transplants with Sustained Graft and Patient Benefits

AMERICAN JOURNAL OF TRANSPLANTATION, Issue 6 2009
L. Li
Despite early promising patient and graft outcomes with steroid-free (SF) immunosuppression in pediatric kidney transplant recipients, data on long-term safety and efficacy results are lacking. We present our single-center experience with 129 consecutive pediatric kidney transplant recipients on SF immunosuppression, with a mean follow-up of 5 years. Outcomes are compared against a matched cohort of 57 concurrent recipients treated with steroid-based (SB) immunosuppression. In the SF group, 87% of kidney recipients with functioning grafts remain corticosteroid - free. Actual intent-to-treat SF (ITT-SF) and still-on-protocol SF patient survivals are 96% and 96%, respectively, actual graft survivals for both groups are 93% and 96%, respectively and actual death-censored graft survivals for both groups are 97% and 99%, respectively. Unprecedented catch-up growth is observed in SF recipients below 12 years of age. Continued low rates of acute rejection, posttransplant diabetes mellitus (PTDM), hypertension and hyperlipidemia are seen in SF patients, with sustained benefits for graft function. In conclusion, extended enrollment and longer experience with SF immunosuppression for renal transplantation in low-risk children confirms protocol safety, continued benefits for growth and graft function, low acute rejection rates and reduced cardiovascular morbidity. [source]

Identifying Specific Causes of Kidney Allograft Loss

AMERICAN JOURNAL OF TRANSPLANTATION, Issue 3 2009
Z. M. El-Zoghby
The causes of kidney allograft loss remain unclear. Herein we investigated these causes in 1317 conventional kidney recipients. The cause of graft loss was determined by reviewing clinical and histologic information the latter available in 98% of cases. During 50.3 ± 32.6 months of follow-up, 330 grafts were lost (25.0%), 138 (10.4%) due to death with function, 39 (2.9%) due to primary nonfunction and 153 (11.6%) due to graft failure censored for death. The latter group was subdivided by cause into: glomerular diseases (n = 56, 36.6%); fibrosis/atrophy (n = 47, 30.7%); medical/surgical conditions (n = 25, 16.3%); acute rejection (n = 18, 11.8%); and unclassifiable (n = 7, 4.6%). Glomerular pathologies leading to failure included recurrent disease (n = 23), transplant glomerulopathy (n = 23) and presumed nonrecurrent disease (n = 10). In cases with fibrosis/atrophy a specific cause(s) was identified in 81% and it was rarely attributable to calcineurin inhibitor (CNI) toxicity alone (n = 1, 0.7%). Contrary to current concepts, most cases of kidney graft loss have an identifiable cause that is not idiopathic fibrosis/atrophy or CNI toxicity. Glomerular pathologies cause the largest proportion of graft loss and alloinmunity remains the most common mechanism leading to failure. This study identifies targets for investigation and intervention that may result in improved kidney transplantation outcomes. [source]

Kidney Transplantation in Previous Heart or Lung Recipients

AMERICAN JOURNAL OF TRANSPLANTATION, Issue 3 2009
B. E. Lonze
Outcomes after heart and lung transplants have improved, and many recipients survive long enough to develop secondary renal failure, yet remain healthy enough to undergo kidney transplantation. We used national data reported to United Network for Organ Sharing (UNOS) to evaluate outcomes of 568 kidney after heart (KAH) and 210 kidney after lung (KAL) transplants performed between 1995 and 2008. Median time to kidney transplant was 100.3 months after heart, and 90.2 months after lung transplant. Renal failure was attributed to calcineurin inhibitor toxicity in most patients. Outcomes were compared with primary kidney recipients using matched controls (MC) to account for donor, recipient and graft characteristics. Although 5-year renal graft survival was lower than primary kidney recipients (61% KAH vs. 73.8% MC, p < 0.001; 62.6% KAL vs. 82.9% MC, p < 0.001), death-censored graft survival was comparable (84.9% KAH vs. 88.2% MC, p = 0.1; 87.6% KAL vs. 91.8% MC, p = 0.6). Furthermore, renal transplantation reduced the risk of death compared with dialysis by 43% for KAH and 54% for KAL recipients. Our findings that renal grafts function well and provide survival benefit in KAH and KAL recipients, but are limited in longevity by the general life expectancy of these recipients, might help inform clinical decision-making and allocation in this population. [source]

Recovery Factors Affecting Utilization of Small Pediatric Donor Kidneys

AMERICAN JOURNAL OF TRANSPLANTATION, Issue 1 2009
L. K. Kayler
Kidneys from small pediatric donors are underutilized. Using data from the Scientific Registry of Transplant Recipients for donors <21 kg in which at least one organ was recovered from 1997 to 2007 (n = 3341), donor and recovery factors were evaluated by multivariate analysis for associations with (a) kidney nonrecovery and (b) transplantation of recovered kidneys. Results: The proportion of kidney recoveries were 55% during liver procurements and 40% during intestine procurements amongst donors <10 kg (p < 0.01) compared to 93% and 88%, respectively, for donors weighing 10,20 kg (p = 0.003). Intestine procurement was independently associated with an 81% greater likelihood of kidney nonrecovery (p < 0.0001) and a 48% lower likelihood of transplantation (p = 0.0004). A multivariate Cox model indicated that single kidney recipients had a 63% higher risk of graft failure compared with en bloc kidney recipients (p < 0.0001); however, concurrent intestine recovery was not a significant risk factor for graft loss. Intestine recovery from donors <21 kg of age is strongly associated with higher kidney nonrecovery and lower transplantation rates. Graft survival is worse with single kidney transplantation, but is not significantly affected by intestine recovery. Small pediatric donors procurement teams should strive to increase kidney recoveries overall and en bloc recoveries in particular. [source]

The Effect of Sirolimus on Prostate-Specific Antigen (PSA) Levels in Male Renal Transplant Recipients Without Prostate Cancer

AMERICAN JOURNAL OF TRANSPLANTATION, Issue 12 2008
K. Chamie
In kidney recipients, the immunosuppressant sirolimus has been associated with a decreased incidence of de novo posttransplant malignancies (including prostate cancer). But the effect of sirolimus on the prostate-specific antigen (PSA) blood level, an important prostate cancer screening tool, remains unknown. We studied male kidney recipients >50 years old (transplanted from January 1994 to December 2006) without clinical evidence for prostate cancer. Pre- and posttransplant PSA levels were analyzed for 97 recipients (n = 19 on sirolimus, n = 78 on tacrolimus [control group]). Pretransplant PSA was similar for sirolimus versus tacrolimus recipients (mean, 1.8 versus 1.7 ng/mL, p = 0.89), but posttransplant PSA was significantly lower for recipients on sirolimus (mean, 0.9 versus 1.9 ng/mL, respectively, p < 0.001). The mean difference between pretransplant and posttransplant PSA was ,0.9 ng/mL (50.0%, p = 0.006) for the sirolimus group versus +0.2 ng/mL (+11.8%, p = 0.24) for the tacrolimus group. By multivariate analysis, only pretransplant PSA and immunosuppression with sirolimus independently impacted posttransplant PSA. Our data strongly suggest that sirolimus is associated with a significant PSA decrease in kidney recipients. Future studies must investigate the clinical implications of our findings for the use of PSA for prostate cancer screening in male kidney recipients on sirolimus. [source]

Prospective Monitoring of Polyomavirus BK Replication and Impact of Pre-Emptive Intervention in Pediatric Kidney Recipients

Identifying High Risk Groups and Quantifying Absolute Risk of Cancer After Kidney Transplantation: A Cohort Study of 15 183 Recipients

AMERICAN JOURNAL OF TRANSPLANTATION, Issue 9 2007
A. C. Webster
Transplant recipients have increased cancer risk, but data on risk variation across different patient groups are sparse. Rates and standardized rate ratios (SRR) of cancer (all sites, excluding nonmelanocytic skin and lip cancer) compared to the general population were calculated, using Australia and New Zealand Dialysis and Transplant Registry data. Within the transplant population, risk factors were identified (hazard ratios: HR; 95% CI) and absolute risk estimated for recipient groups. A total of 1642 (10.8%) of 15 183 recipients developed cancer. Risk was inversely related to age (SRR 15,30 children, 2 if >65 years). Females aged 25,29 had rates equivalent to women aged 55,59 from the general population. Age trend for lymphoma, colorectal and breast risk was similar; melanoma showed less variability across ages, prostate showed no risk increase. Within the transplanted population, risk was affected by age differently for each sex (p = 0.007), elevated by prior malignancy (HR 1.40; 1.03,1.89), white race (HR 1.36; 1.12,1.89), but reduced by diabetic end-stage kidney disease (ESKD) (HR 0.67; 0.50,0.89). Cancer rates in kidney recipients are similar to nontransplanted people 20,30 years older, but absolute risk differs across patient groups. Men aged 45,54 surviving 10 years have cancer risks varying from 1 in 13 (non-white, no prior cancer, diabetic ESKD) to 1 in 5 (white, prior cancer, other ESKD). [source]

Thymoglobulin-Associated Cd4+ T-Cell Depletion and Infection Risk in HIV-Infected Renal Transplant Recipients

AMERICAN JOURNAL OF TRANSPLANTATION, Issue 4 2006
J.T. Carter
HIV-infected patients are increasingly referred for kidney transplantation, and may be at an increased risk for rejection. Treatment for rejection frequently includes thymoglobulin. We studied thymoglobulin's effect on CD4+ T-cell count, risk of infection and rejection reversal in 20 consecutive HIV-infected kidney recipients. All patients used antiretroviral therapy and opportunistic infection prophylaxis. Maintenance immunosuppression consisted of prednisone, mycophenolate mofetil and cyclosporine. Eleven patients received thymoglobulin (7 for rejection and 4 for delayed/slow graft function) while 9 did not. These two groups were similar in age, gender, race, donor characteristics and immunosuppression. Mean CD4+ T-cell counts remained stable in patients who did not receive thymoglobulin, but became profoundly suppressed in those who did, decreasing from 475 ± 192 to 9 ± 10 cells/,L (p < 0.001). Recovery time ranged from 3 weeks to 2 years despite effective HIV suppression. Although opportunistic infections were successfully suppressed, low CD4+ T-cell count was associated with increased risk of serious infections requiring hospitalization. Rejection reversed in 6 of 7 patients receiving thymoglobulin. We conclude that thymoglobulin reverses acute rejection in HIV-infected kidney recipients, but produces profound and long-lasting suppression of the CD4+ T-cell count associated with increased risk of infections requiring hospitalization. [source]

Alemtuzumab Induction and Sirolimus Plus Mycophenolate Mofetil Maintenance for CNI and Steroid-Free Kidney Transplant Immunosuppression

AMERICAN JOURNAL OF TRANSPLANTATION, Issue 12 2005
S. M. Flechner
We performed a pilot study in which 22 kidney recipients (14 LD: 8 DCD) were given alemtuzumab induction (30 mg day 0 and 1), steroids (500 mg mp day 0 and 1, none thereafter), mycophenolate mofetil (MMF) maintenance (500 mg b.i.d) and sirolimus (concentration controlled 8,12 ng/mL). With a mean follow-up of 15.9 months, patient survival is (21/22) 96% and graft survival (19/22) 87%. Acute rejections occurred in (8) 36.3% (two humoral). Of 19 surviving grafts, 18 (95%) remain steroid and 15 (79%) CNI-free. At 1 year, mean creatinine was 1.43 mg/dL. Overall infection rates were low, but 2 patients developed severe acute respiratory distress syndrome (ARDS) at month 3 and 7, respectively, resulting in mortality in one and a graft loss in the other. No cancer or PTLD was observed. Leukopenia was common and MMF dose was reduced or eliminated in 6/22 (27%) patients. The reported higher than expected rate of acute rejection, leukopenia and possible pulmonary toxicity suggests excessive morbidity. Modifications such as an initial period of CNI use should be considered. [source]