Sunday, June 30, 2013

Incidence of Tuberculosis in Deceased-Organ Donors and Transmission Risk to Recipients in Spain

Transplantation - Published Ahead-of-Print Incidence of Tuberculosis in Deceased-Organ Donors and Transmission Risk to Recipients in Spain

Background: Globalization and migration patterns have increased the number of donors from countries with high incidence rates of tuberculosis (TB) in low incidence countries, with the subsequent increase in risk of TB transmission to the recipients. Methods: Retrospective cohort study, including all actual deceased donors in Spanish hospitals between January 1998 and June 2011 and all the recipients who had received an organ from donors identified as TB cases. Results: Six actual donors were identified as TB cases, representing an annual incidence of 30.6 cases/100,000 donors (95% CI, 4-58). Two cases did not become utilized donors, because TB was detected in the organ recovery and were therefore excluded. Annual incidence in utilized donors was 23 cases/100,000 donors (95% CI, 6-59). Annual incidence of the Spanish population in the same period was 17.5 cases/100,000 inhabitants (95% CI, 17-18). Annual incidence in actual donors belonging to the Romanian immigrant community was 2353 cases/100,000 donors (95% CI, 286-8242). Variations in the prophylactic strategy utilized in recipients were observed. TB was transmitted to three recipients (27.3% transmission), two of whom developed active TB. Conclusions: Incidence of TB in actual donors is greater than that of the general population (P<0.001). The risk of immigrant communities should be grouped according to the real incidence in donors. Transmissibility of TB is high; therefore, transplant teams should be immediately informed when TB donor transmission is suspected to prevent TB in the recipient. (C) 2013 Lippincott Williams & Wilkins, Inc.


http://pdfs.journals.lww.com/transplantjournal/9000/00000/Incidence_of_Tuberculosis_in_Deceased_Organ_Donors.98547.pdf

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Impact of Early Graft Function on 10-Year Graft Survival in Recipients of Kidneys From Standard- or Expanded-Criteria Donors

Transplantation - Published Ahead-of-Print Impact of Early Graft Function on 10-Year Graft Survival in Recipients of Kidneys From Standard- or Expanded-Criteria Donors

Background: The use of kidneys from expanded-criteria donors (ECD) is regarded with caution. Methods: We compared 279 kidney transplant recipients (KTxR) from standard-criteria donors (SCD) and 237 from ECD, transplanted between January 1990 and December 2006. We evaluated the impact of immediate graft function (IGF), slow graft function (SGF), and delayed graft function (DGF) and the drop in estimated glomerular filtration rate ([DELTA]eGFR) <=30% or >30% during the first year after transplantation on long-term patient and death-censored graft survival (DCGS). Results: Ten-year patient survival was similar in SCD- or ECD-KTxR (P=0.38). DCGS was better in SCD-KTxR versus ECD-KTxR (77.3% vs. 67.3%; P=0.01). DCGS did not differ in either group experiencing IGF (P=0.17) or DGF (P=0.12). However, DCGS was worse in ECD-KTxR experiencing SGF (84.9% vs. 73.7%; P=0.04). Predictors of DCGS were 1-year serum creatinine (hazard ratio, 1.03; P<0.0001) and [DELTA]eGFR >30% between 1 and 12 months ([DELTA]1-12eGFR) after transplantation (hazard ratio, 2.2; P=0.02). In ECD-KTxR with IGF and more than 1-year follow-up, 10-year DCGS was better in those with [DELTA]1-12eGFR <=30% versus those with [DELTA]1-12eGFR >30% (83.8% vs. 53.6%; P=0.01). Conclusion: Recipients of SCD or ECD kidneys with IGF or DGF had similar 10-year patient survival and DCGS. SGF had a worse impact on DCGS in ECD-KTxR. In addition to 1-year serum creatinine, [DELTA]1-12eGFR >30% is a negative predictor of DCGS. Larger studies should confirm if increasing the use of ECD, avoiding factors that contribute to SGF or DGF, and/or a decline in eGFR during the first year after transplantation may expand the donor pool and result in acceptable long-term outcomes. (C) 2013 Lippincott Williams & Wilkins, Inc.


http://pdfs.journals.lww.com/transplantjournal/9000/00000/Impact_of_Early_Graft_Function_on_10_Year_Graft.98552.pdf

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Comparison of Pharmacokinetics and Pathology for Low-Dose Tacrolimus Once-Daily and Twice-Daily in Living Kidney Transplantation: Prospective Trial in Once-Daily Versus Twice-Daily Tacrolimus

Transplantation - Published Ahead-of-Print Comparison of Pharmacokinetics and Pathology for Low-Dose Tacrolimus Once-Daily and Twice-Daily in Living Kidney Transplantation: Prospective Trial in Once-Daily Versus Twice-Daily Tacrolimus

Background: A prolonged-release formulation of tacrolimus (Tacrolimus QD) was developed to allow once-daily dosing and to have similar safety and efficacy profiles to twice-daily tacrolimus (Tacrolimus BID). This study compared the pharmacokinetics (PK) and renal pathology by protocol biopsy in de novo living kidney transplant recipients treated with either low-dose Tacrolimus QD or Tacrolimus BID. Methods: Between November 2009 and January 2011, 102 consecutive adult patients were randomized to receive either low-dose Tacrolimus QD or Tacrolimus BID. All patients underwent PK study and protocol biopsy on postoperative day 14. Additional protocol biopsies were performed between 6 and 12 months after renal transplantation. Results: During the 1-year follow up, the incidence of biopsy-proven acute rejection and toxic tubulopathy was low and similar in both groups. Twenty-four hours area under the curve (AUC0-24) was not different in both groups (285+/-78.7 and 281+/-62.4 ng hr/mL in Tacrolimus QD and Tacrolimus BID, respectively). C0 was well correlated with AUC0-24 in both groups and AUC0-24 between 260 and 280 in the Tacrolimus QD group was achieved by 6 to 8 ng/mL of C0. Acute nephrotoxicity was less than 10% in both groups without any clinical manifestation. Conclusion: Clinical efficacy, safety, and PK profile of Tacrolimus QD is same as those of Tacrolimus BID. (C) 2013 Lippincott Williams & Wilkins, Inc.


http://pdfs.journals.lww.com/transplantjournal/9000/00000/Comparison_of_Pharmacokinetics_and_Pathology_for.98539.pdf

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Friday, June 28, 2013

Ureterostomy cytomegalovirus infection presenting as stoma ulceration in a kidney allograft receptor: a case report

[Ureterostomy cytomegalovirus infection presenting as stoma ulceration in a kidney allograft receptor: a case report].

Abstract

Cytomegalovirus (CMV) is the most common viral infection affecting transplant patients, but urinary tract involvement has been rare. Only a few cases of symptomatic ureteritis have been reported in renal transplant recipients. In previous reports the presentation of CMV ureteritis is obstructive nephropathy, often in the absence of systemic illness, or rarely it may also mimic allograft rejection with minimal obstructive symptoms. We describe an additional case of CMV ureteritis in a patient with cutaneous ureterostomy. The unusual clinical presentation with urinary infection symptoms and ureterostomy stoma ulceration constitute a very particular presentation. The increasing report cases with CMV ureteritis suggest an increase of this post-transplant complication.

Links

Authors

Rico JE, Cardona X, Rodelo J, Reino A, Arias LF, Arbeláez M

Institution

Sección de Nefrología y Grupo de Trasplante Renal, Universidad de Antioquía, Hospital Universitario San Vicente de Paúl, Medillín, Colombia. jorgericof@yahoo.com

Source

Actas Urol Esp 2008 Jun; 32(6):649-52.

MeSH

  • Adult
  • Cytomegalovirus Infections
  • Humans
  • Inflammation
  • Kidney Transplantation
  • Male
  • Skin Ulcer
  • Ureteral Diseases
  • Ureterostomy

Pub Type(s)

Case Reports; English Abstract; Journal Article

Language

spa

PubMed ID

18655351

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Survival of renal transplantation patients older than 60 years: a single-center experience.

Survival of renal transplantation patients older than 60 years: a single-center experience.

Abstract

BACKGROUND

Elderly patients are the fastest growing population requiring renal replacement therapy. It has been stated that renal transplantation may be the best treatment option for these patients. However, it has been observed that older patients have a higher mortality rate than those who are younger. Yet the factors that determine post-transplantation outcomes in this population remain poorly defined. The aims of this study were to evaluate the graft and patient survival in kidney transplant recipients who are older than 60 years of age to identify relevant predictive factors.

METHODS

In this population-based retrospective cohort study of 201 kidney transplantations performed in elderly patients from January 2002 throughout June 2009, we estimated the 1-,3-,and 5-year patients and graft survival rates. We also evaluated the complications and the predictors of poor outcomes. Survival times were analyzed using the Kaplan-Meier method and survival differences assessed with Mantel-Cox log rank-test. We performed a Cox proportional hazards regression models to evaluate the impact of baseline and treatment characteristics on patient and graft survival.

RESULTS

Graft and patient survival rates at 1, 3, and 5 years were 76.4%, 71.3%, and 54.3%, and 78.2%, 73.8%, and 56.4%, respectively. Graft survival rates censored for patient death with a functioning graft were 93.1, 92.1, and 89%. Patient survival rates differed between diabetic and nondiabetic subjects at 1, 3 and 5 years (69.5% versus 83.6%; 59.8% versus 72.3%; 43.6% versus 65.7%; P = .008). On multivariate analysis, the factors associated with patients survival were diabetes mellitus (hazard ratio [HR] 2.058, 95% confidence interval [CI] 1.173-3.611, P = .012) and the 1-month serum creatinine value was > 1.6 mg/dL (HR 2.108 for each point increase, 95% CI 1.521-2.921, P = .000). Furthermore, there was an insignificant trend forward an association between active or past smoker and lower patient survival (HR 1.689, 95% CI 0.937-3.043, P = .08). The main causes of graft loss were patient death (79.5%). acute rejection (6.8%), and chronic allograft nephropathy (5.5%).

CONCLUSION

Renal transplantation can be performed safely and with acceptable outcomes in elderly patients after appropriate clinical evaluation. The grafts show excellent survival albeit that deaths with a functional graft continue to be an important issue.

Links

Authors

Rodelo JR, Nieto-Ríos JF, Serna-Higuita LM, Henao JE, García A, Reino AC, Tobón JC, Arbeláez M

Institution

Transplant Group, Nephrology Division, Universidad de Antioquia and Hospital Pablo Tobón Uribe, Medellin, Colombia. Electronic address: jrodelo@une.net.co.

Source

Transplant. Proc. 2013 May; 45(4):1402-9.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

23726583

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Cost-effectiveness analysis of the early conversion of tacrolimus to mammalian target of rapamycin inhibitors in patients with renal transplantation


1. Transplant Proc. 2011 Nov;43(9):3367-76. doi: 10.1016/j.transproceed.2011.09.092.

Cost-effectiveness analysis of the early conversion of tacrolimus to mammalian
target of rapamycin inhibitors in patients with renal transplantation.

Gamboa O, Montero C, Mesa L, Benavides C, Reino A, Torres RE, Castillo JS.

Fundaci�n Esensa, Bogot�, Colombia. oa_gamboa@yahoo.es

BACKGROUND: Renal replacement therapies which consist of renal transplantation
and dialysis are the only treatment options for patients with terminal renal
failure. These therapies have changed the outcome from being fatal to being a
chronic disease. Kidney transplantation involves the use of immunosuppressive
agents to prevent rejection. Currently, several immunosuppressive agents have
shown efficacy, safety, and different costs.
OBJECTIVE: The aim was to evaluate the cost-effectiveness of early conversion
from tacrolimus to mammalian target of rapamycin inhibitors sirolimus or
everolimus versus continuous treatment with tacrolimus among renal transplantat
patients in Colombia.
METHODS: We performed systematic literature review to extract data for clinical
effectiveness and safety of tacrolimus replacement schemes for immunosuppressive
therapy in renal transplantation in adults. A Markov model in TreeAge was
developed, simulating the patient's natural history with renal transplantation.
The perspective of the Colombian Health System was used, including only direct
costs. The cost-effectiveness ratio and incremental cost-effectiveness ratio were
estimated. Deterministic and probabilistic sensitivity analyses were performed. A
5% discount rate was applied in costs and health results.
RESULTS: Results for the replacement of tacrolimus to sirolimus are provided. The
cost per year of additional life gained for sirolimus was Col$2,441,171.43; the
cost for avoided loss was Col$4,014,152.84. The acceptability curve shows that a
strategy with sirolimus is the most cost-effective one.
CONCLUSIONS: This study suggested that the sirolimus strategy is cost-effective
in Colombia for patients with renal transplantation using as threshold less than
three times the gross domestic product (GDP) per capita of Colombia per life of
years gained.

Copyright � 2011 Elsevier Inc. All rights reserved.

PMID: 22099798 [PubMed - in process]

Cost-effectiveness analysis of the early conversion of tacrolimus to mammalian target of rapamycin inhibitors in patients with renal transplantation.

Abstract

BACKGROUND

Renal replacement therapies which consist of renal transplantation and dialysis are the only treatment options for patients with terminal renal failure. These therapies have changed the outcome from being fatal to being a chronic disease. Kidney transplantation involves the use of immunosuppressive agents to prevent rejection. Currently, several immunosuppressive agents have shown efficacy, safety, and different costs.

OBJECTIVE

The aim was to evaluate the cost-effectiveness of early conversion from tacrolimus to mammalian target of rapamycin inhibitors sirolimus or everolimus versus continuous treatment with tacrolimus among renal transplantat patients in Colombia.

METHODS

We performed systematic literature review to extract data for clinical effectiveness and safety of tacrolimus replacement schemes for immunosuppressive therapy in renal transplantation in adults. A Markov model in TreeAge was developed, simulating the patient's natural history with renal transplantation. The perspective of the Colombian Health System was used, including only direct costs. The cost-effectiveness ratio and incremental cost-effectiveness ratio were estimated. Deterministic and probabilistic sensitivity analyses were performed. A 5% discount rate was applied in costs and health results.

RESULTS

Results for the replacement of tacrolimus to sirolimus are provided. The cost per year of additional life gained for sirolimus was Col$2,441,171.43; the cost for avoided loss was Col$4,014,152.84. The acceptability curve shows that a strategy with sirolimus is the most cost-effective one.

CONCLUSIONS

This study suggested that the sirolimus strategy is cost-effective in Colombia for patients with renal transplantation using as threshold less than three times the gross domestic product (GDP) per capita of Colombia per life of years gained.

Links

Authors

Gamboa O, Montero C, Mesa L, Benavides C, Reino A, Torres RE, Castillo JS

Institution

Fundación Esensa, Bogotá, Colombia. oa_gamboa@yahoo.es

Source

Transplant. Proc. 2011 Nov; 43(9):3367-76.

Pub Type(s)

Journal Article; Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

22099798

Provided by




Everolimus leads to a lower risk of BKV viremia than mycophenolic acid in de novo renal transplantation patients: a single-center experience

Clinical Transplantation Everolimus leads to a lower risk of BKV viremia than mycophenolic acid in de novo renal transplantation patients: a single-center experience

Abstract

Background

There are limited published data concerning the effects of different immunosuppressive regimens on the development of polyomavirus (BKV) viremia. We examined the risk of developing BKV viremia in kidney transplant recipients receiving everolimus (EVR) or mycophenolic acid (MPA) as maintenance therapy.

Methods

We observationally analyzed 296 patients who underwent renal transplantation at our center between 2005 and 2010: 58 were treated with EVR and low-dose cyclosporine (LD-CyA) (group 1) and 238 with MPA and standard-dose CyA (group 2). All of the patients received induction therapy with basiliximab and maintenance steroids. BKV viremia (a whole-blood viral load of >850 copies/mL) was measured by means of real-time polymerase chain reaction at least once a month during a 12-month follow-up period.

Results

BKV viremia was detected in 57 patients (19%), five (9%) in group 1 and 52 (22%) in group 2. Kaplan–Meier analyses showed that freedom from BKV viremia was significantly more frequent in group 1. The mean time of onset of BKV viremia was about four months after transplantation in both groups. The median viral load was greater in group 2 (12.5 ± 6.1 vs. 2.5 ± 1.8 × 104 copies/mL; p = 0.01). After the onset of BKV viremia, graft function significantly declined in group 2: 11 patients developed polyomavirus-associated nephropathy (PVAN) and four presumptive PVAN; nine experienced an acute rejection after the discontinuation of MPA, and 11 (21%) lost their graft. There was no graft loss in group 1.

Conclusion

These findings suggest that in comparison with MPA and Cya, an EVR and LD-CyA regimen lowers the risk of BKV viremia after kidney transplantation and favorably alters outcomes.




http://onlinelibrary.wiley.com/resolve/doi?DOI=10.1111%2Fctr.12151


Thursday, June 27, 2013

Contribution of Interferon-γ Release Assays (IGRAs) to the Diagnosis of Latent Tuberculosis Infection After Renal Transplantation

Transplantation - Most Popular Articles
imageBackground: Renal transplant recipients (RTRs), as all immunosuppressed patients, are at increased risk of reactivating latent tuberculosis infection (LTBI). Detecting LTBI in this population is therefore important to prevent active TB. The tuberculin skin test (TST) has a poor sensitivity in this setting. Methods: The aim of this prospective study was to compare the diagnostic performance of the TST and two interferon-γ release assays (IGRAs): T-SPOT.TB (Oxford Immunotec, Oxford, UK) and QuantiFERON Gold In-Tube (QGIT; Cellestis, Australia), performed simultaneously, for the detection of patients with risk factors for LTBI or a definite history of TB among RTRs under stable immunosuppression. Results: Two hundred five patients (ages 59±13 years, tested 10.4±7.1 years after transplantation) were studied. Positivity rate was 4.5% for TST, 20.5% for T-SPOT.TB, and 23.5% for QGIT. Agreement between IGRAs was fair (κ=0.71). Sensitivity of T-SPOT.TB and QGIT for detection of prior active TB was 55.6% (95% confidence interval [CI], 21.2–86.3) and 44.4 (95% CI, 13.7–78.8), respectively. Sensitivity of both IGRAs for detection of risk factors for LTBI was 33.3% (95% CI, 19.6–49.5). Specificity was 85.5% (95% CI, 78.9–90.7) for T-SPOT.TB and 80.1% (95% CI, 72.9–86.2) for QGIT. Combining IGRAs did not significantly improve sensitivity. Conclusions: Because their sensitivity for detecting prior active TB and probable LTBI in RTRs is very low, IGRAs cannot be used to exclude LTBI. These results emphasize the limitations of IGRAs in the setting of chronic immunosuppressive therapy.

Tuesday, June 25, 2013

Nighttime procedures are not associated with adverse outcomes in kidney transplantation [feedly]


 
 
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Nighttime procedures are not associated with adverse outcomes in kidney transplantation
Surgeries performed during the night are associated with higher complication rates. The aim of this study was to determine the impact of nighttime surgery on the outcome after kidney transplantation. In all, 873 deceased donor kidney transplants were retrospectively analyzed and grouped according to the time of surgery: daytime (8 am to 8 pm, n = 610) versus nighttime (8 pm to 8 am, n = 263). Statistical analysis compared patient/graft survival, rate of delayed graft function (DGF), acute rejection rate, and surgical complications. One and 5-year patient and graft survival did not differ between daytime and nighttime transplants. DGF occurred in 31.1% of daytime compared to 37.6% of nighttime procedures (P = 0.06). Acute allograft rejection was observed in 22.6% of daytime compared to 18.3% in nighttime graft recipients (P = 0.15). Nighttime procedures were associated with 22.4% complications compared to 22.1% in daytime procedures (P = 0.92). Most importantly, if transplantations were postponed until the next morning, cold ischemia time (CIT) would have increased from 16.6 h to 24.6 h (P < 0.0001) which would have resulted in decreased long-term survival (P < 0.02). Nighttime kidney transplants are neither associated with a higher surgical complication rate nor worse 5-year outcomes than daytime procedures, thus are justified to keep CIT short.

Friday, June 21, 2013

Association Between Steroid Dosage and Death With a Functioning Graft After Kidney Transplantation. [feedly]


 
 
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Association Between Steroid Dosage and Death With a Functioning Graft After Kidney Transplantation.
Death with a functioning graft remains a major challenge following kidney transplantation. Steroid dosing may be a modifiable risk factor. Collaborative Transplant Study (CTS) data were analyzed to assess the relationship between long-term steroid dose and death with function during years 2-5 posttransplant in 41 953 adult recipients of a deceased-donor kidney transplant during 1995-2010. Steroid dose at year 1 correlated significantly with death with function overall, and with death due to cardiovascular disease or infection (all p < 0.001). In patients with optimal graft function (serum creatinine <130 µmol/L) and no anti-rejection treatment during (a) year 1 (b) years 1 and 2, these significant associations remained (all p < 0.001). The center-specific incidence of steroid withdrawal during year 2 showed a significant inverse association with death due to cardiovascular disease (p < 0.001) or infection (p < 0.001) overall, and within the subpopulation with good graft function and no rejection during year 1 (p = 0.002 and p < 0.001, respectively). Maintenance steroid dose shows a highly significant association with death with a functioning graft caused by cardiovascular disease or infection during years 2-5 after kidney transplantation, even in patients with good graft outcomes in whom steroid treatment would appear to be unnecessary.

Eculizumab Improves Posttransplant Thrombotic Microangiopathy Due to Antiphospholipid Syndrome Recurrence but Fails to Prevent Chronic Vascular Changes. [feedly]


 
 
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Eculizumab Improves Posttransplant Thrombotic Microangiopathy Due to Antiphospholipid Syndrome Recurrence but Fails to Prevent Chronic Vascular Changes.
Thrombotic microangiopathy (TMA) is one of the hallmark vascular lesions of antiphospholipid syndrome nephropathy (APSN). These lesions are at high risk of recurrence after kidney transplantation. The complement pathway is thought to be active in this process. We used eculizumab to treat three consecutive kidney transplant recipients with posttransplant TMA due to APSN recurrence that was resistant to plasmapheresis and explored the complement deposition and apoptotic and vascular cell markers on the sequential transplant biopsies. Treatment with eculizumab resulted in a rapid and dramatic improvement of the graft function in all three patients and in improvement of the TMA lesions within the graft. None of these patients had TMA flares after eculizumab was withdrawn. At the time of TMA diagnosis, immunofluorescence studies revealed intense C5b-9 and C4d depositions at the endothelial cell surface of the injured vessels. Moreover, C5b-9 colocalized with vessels exhibiting a high rate of apoptotic cells. Examination of sequential biopsies during eculizumab therapy showed that TMA lesions, C4d and apoptotic markers were rapidly cleared but the C5b-9 deposits persisted for several months as a footprint of the TMA. Finally, we noticed that complement inhibition did not prevent the development of the chronic vascular changes associated with APSN. Eculizumab seems to be an efficient method for treating severe forms of posttransplant TMA due to APSN recurrence. Terminal complement inhibition does not prevent the development of chronic APSN.

Thursday, June 6, 2013

Two Patients With History of STEC-HUS, Posttransplant Recurrence and Complement Gene Mutations. [feedly]


 
 
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Two Patients With History of STEC-HUS, Posttransplant Recurrence and Complement Gene Mutations.
Hemolytic uremic syndrome (HUS) is a disease of microangiopathic hemolytic anemia, thrombocytopenia and acute renal failure. About 90% of cases are secondary to infections by Escherichia coli strains producing Shiga-like toxins (STEC-HUS), while 10% are associated with mutations in genes encoding proteins of complement system (aHUS). We describe two patients with a clinical history of STEC-HUS, who developed end-stage renal disease (ESRD) soon after disease onset. They received a kidney transplant but lost the graft for HUS recurrence, a complication more commonly observed in aHUS. Before planning a second renal transplantation, the two patients underwent genetic screening for aHUS-associated mutations that revealed the presence of a heterozygous CFI mutation in patient #1 and a heterozygous MCP mutation in patient #2, and also in her mother who donated the kidney. This finding argues that the two cases originally diagnosed as STEC-HUS had indeed aHUS triggered by STEC infection on a genetic background of impaired complement regulation. Complement gene sequencing should be performed before kidney transplantation in patients who developed ESRD following STEC-HUS since they may be undiagnosed cases of aHUS, at risk of posttransplant recurrence. Furthermore, genetic analysis of donors is mandatory before living-related transplantation to exclude carriers of HUS-predisposing mutations.

Two Patients With History of STEC-HUS, Posttransplant Recurrence and Complement Gene Mutations. [feedly]


 
 
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Two Patients With History of STEC-HUS, Posttransplant Recurrence and Complement Gene Mutations.
Hemolytic uremic syndrome (HUS) is a disease of microangiopathic hemolytic anemia, thrombocytopenia and acute renal failure. About 90% of cases are secondary to infections by Escherichia coli strains producing Shiga-like toxins (STEC-HUS), while 10% are associated with mutations in genes encoding proteins of complement system (aHUS). We describe two patients with a clinical history of STEC-HUS, who developed end-stage renal disease (ESRD) soon after disease onset. They received a kidney transplant but lost the graft for HUS recurrence, a complication more commonly observed in aHUS. Before planning a second renal transplantation, the two patients underwent genetic screening for aHUS-associated mutations that revealed the presence of a heterozygous CFI mutation in patient #1 and a heterozygous MCP mutation in patient #2, and also in her mother who donated the kidney. This finding argues that the two cases originally diagnosed as STEC-HUS had indeed aHUS triggered by STEC infection on a genetic background of impaired complement regulation. Complement gene sequencing should be performed before kidney transplantation in patients who developed ESRD following STEC-HUS since they may be undiagnosed cases of aHUS, at risk of posttransplant recurrence. Furthermore, genetic analysis of donors is mandatory before living-related transplantation to exclude carriers of HUS-predisposing mutations.

Wednesday, June 5, 2013

Outcomes after kidney transplantation of patients previously diagnosed with atrial fibrillation. [feedly]


 
 
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Outcomes after kidney transplantation of patients previously diagnosed with atrial fibrillation.
Little is known about the prevalence and outcomes of patients with atrial fibrillation/flutter (AF) who receive a kidney transplant. We identified all patients who had >1 year of uninterrupted Medicare A+B coverage before receiving their first kidney transplant (1997-2009). The presence of pretransplant AF was ascertained from diagnosis codes in Medicare physician claims. We studied the posttransplant outcomes of death, all-cause graft failure, death-censored graft failure and stroke using multivariable Cox regression. Of 62 706 eligible first kidney transplant recipients studied, 3794 (6.4%) were diagnosed with AF prior to kidney transplant. Over a mean follow up of 4.9 years, 40.6% of AF patients and 24.9% without AF died. All-cause and death-censored graft failure were 46.8% and 16.5%, respectively, in the AF group and 36.4% and 19.5%, respectively, in those without AF. Ischemic stroke occurred in 2.8% of patients with and 1.6% of patients without AF. In patients with AF, multivariable-adjusted hazard ratios (95% confidence intervals) for death, graft failure, death-censored graft failure and ischemic stroke were 1.46 (1.38-1.54), 1.41 (1.34-1.48), 1.26 (1.15-1.37) and 1.36 (1.10-1.68), respectively. Pre-existing AF is associated with poor posttransplant outcomes. Special attention should be paid to AF in pretransplant evaluation, counseling and risk stratification of kidney transplant candidates.

Alefacept Combined With Tacrolimus, Mycophenolate Mofetil and Steroids in De Novo Kidney Transplantation: A Randomized Controlled Trial [feedly]


 
 
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Alefacept Combined With Tacrolimus, Mycophenolate Mofetil and Steroids in De Novo Kidney Transplantation: A Randomized Controlled Trial

Abstract

Memory T cells play a central role in mediating allograft rejection and are a rational target for immunosuppressive therapy. Alefacept is a recombinant LFA3/IgG1 fusion protein that reduces the number of memory T cells in both psoriatic lesions and the peripheral circulation of psoriasis patients. This study evaluated the efficacy and safety of alefacept compared with placebo when combined with tacrolimus, mycophenolate mofetil and corticosteroids in de novo renal transplant recipients. Between December 2007 and March 2009 patients were randomized in a double-blind fashion to receive alefacept (n = 105) or placebo (n = 107) for 3 months and were then followed for a further 3 months. The primary efficacy endpoint was the incidence of biopsy-confirmed acute T cell mediated rejection (Banff grade ≥1) through Month 6. Memory T cell counts were significantly reduced in the alefacept group from Week 3 to study end compared with placebo. However, there was no significant difference between the alefacept and placebo groups for the primary efficacy endpoint (alefacept, 11.0% vs. placebo, 7.0%, p = 0.3). Patient and graft survival as well as renal function was similar between treatment groups. Safety and tolerability were generally similar between the treatment arms. Malignancy was higher in the alefacept treatment arm.


Cost-Effectiveness of Hand-Assisted Retroperitoneoscopic Versus Standard Laparoscopic Donor Nephrectomy: A Randomized Study [feedly]


 
 
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Cost-Effectiveness of Hand-Assisted Retroperitoneoscopic Versus Standard Laparoscopic Donor Nephrectomy: A Randomized Study
Background: Live kidney donation has a clear economical benefit over dialysis and deceased-donor transplantation. Compared with mini-incision open donor nephrectomy, laparoscopic donor nephrectomy (LDN) is considered cost-effective. However, little is known on the cost-effectiveness of hand-assisted retroperitoneoscopic donor nephrectomy (HARP). This study evaluated the cost-effectiveness of HARP versus LDN. Methods: Alongside a randomized controlled trial, the cost-effectiveness of HARP versus LDN was assessed. Eighty-six donors were included in the LDN group and 82 in the HARP group. All in-hospital costs were recorded. During follow-up, return-to-work and other societal costs were documented up to 1 year. The EuroQol-5D questionnaire was administered up to 1 year postoperatively to calculate quality-adjusted life years (QALYs). Results: Mean total costs from a healthcare perspective were $8935 for HARP and $8650 for LDN (P=0.25). Mean total costs from a societal perspective were $16,357 for HARP and $16,286 for LDN (P=0.79). On average, donors completely resumed their daytime jobs on day 54 in the HARP group and on day 52 in the LDN group (P=0.65). LDN resulted in a gain of 0.005 QALYs. Conclusions: Absolute costs of both procedures are very low and the differences in costs and QALYs between LDN and HARP are very small. Other arguments, such as donor safety and pain, should determine the choice between HARP and LDN. (C) 2013 Lippincott Williams & Wilkins, Inc.