Sexual acquisition of HIV infection after solid organ transplantation: Late presentation and potentially fatal complications.

INTRODUCTION: While the growing knowledge on HIV among solid organ transplant recipients (SOT) is limited to either pretransplant infection or allograft transmission, there are only sparse reports describing HIV-infection after transplantation through sexual route, the primary mode of transmission in the general population. METHODS: From two different centers, we report nine new cases of HIV infection in SOT recipients attributed to sexual acquisition: eight cases of kidney-transplant recipients and one heart-transplant recipient. FINDINGS: There were nine cases of post-transplant HIV-infection detected among 14 526 transplants performed 1998 to 2015. In 6/9 cases, infection was contracted 5 years after SOT. All but one patient had stable allograft function under immunosuppressive therapy. The main trigger to diagnosis was late CMV disease and sexually transmitted diseases; five patients had CDC-stage 3 HIV infection. In 7/9 patients, virologic response and CD4 recovery were achieved within 3 months after starting antiretroviral therapy (ART). After an average of 3.6 years post diagnosis, 5/9 patients remained alive with well-controlled infection and functioning allograft. CONCLUSION: Sexual acquisition of HIV infection after SOT represents a difficult challenge, as it may occur in any kind of transplant and at any time. The course of infection resembles that of the general population, with life-threatening infectious complications, but good response to ART. Assessment of lifestyle and risk behavior is paramount, as indications may be not disclosed without direct questioning.

Melanized fungal infections in kidney transplant recipients: contributions to optimize clinical management.

OBJECTIVES: This is a retrospective and observational study addressing clinical and therapeutic aspects of melanized fungal infections in kidney transplant recipients. METHODS: We retrospectively reviewed medical records of all patients admitted between January 1996 and December 2013 in a single institution who developed infections by melanized fungi. RESULTS: We reported on 56 patients aged between 30 and 74 years with phaeohyphomycosis or chromoblastomycosis (0.54 cases per 100 kidney transplants). The median time to diagnosis post-transplant was 31.2 months. Thirty-four (60.8%) infections were reported in deceased donor recipients. Fifty-one cases of phaeohyphomycosis were restricted to subcutaneous tissues, followed by two cases with pneumonia and one with brain involvement. Most dermatological lesions were represented by cysts (23/51; 45.1%) or nodules (9/51; 17.9%). Exophiala spp. (34.2%) followed by Alternaria spp. (7.9%) were the most frequent pathogens. Graft loss and death occurred in two patients and one patient, respectively. Regarding episodes of subcutaneous phaeohyphomycosis, a complete surgical excision without antifungal therapy was possible in 21 of 51 (41.2%) patients. Long periods of itraconazole were required to treat the other 30 (58.8%) episodes of subcutaneous disease. All four cases of chromoblastomycosis were treated only with antifungal therapy. CONCLUSIONS: Melanized fungal infections should be considered in the differential diagnosis of all chronic skin lesions in transplant recipients. It is suggested that the impact of these infections on graft function and mortality is low. The reduction in immunosuppression should be limited to severely ill patients.

Renal transplantation in human immunodeficiency virus-infected recipients: a case-control study from the Brazilian experience.

BACKGROUND: Highly active antiretroviral therapy has turned human immunodeficiency virus (HIV)-infected patients with end-stage renal disease into suitable candidates for renal transplantation. We present the Brazilian experience with kidney transplantation in HIV-infected recipients observed in a multicenter study. METHODS: HIV-infected kidney transplant recipients and matched controls were evaluated for the incidence of delayed graft function (DGF), acute rejection (AR), infections, graft function, and survival of patients and renal grafts. RESULTS: Fifty-three HIV-infected recipients and 106 controls were enrolled. Baseline characteristics were similar, but a higher frequency of pre-transplant positivity for hepatitis C virus and cytomegalovirus infections was found in the HIV group. Immunosuppressive regimens did not differ, but a trend was observed toward lower use of anti-thymocyte globulin in the group of HIV-infected recipients (P = 0.079). The HIV-positive recipient group presented a higher incidence of treated AR (P = 0.036) and DGF (P = 0.044). Chronic Kidney Disease Epidemiology Collaboration estimated that glomerular filtration rate was similar at 6 months (P = 0.374) and at 12 months (P = 0.957). The median number of infections per patient was higher in the HIV-infected group (P = 0.018). The 1-year patient survival (P < 0.001) and graft survival (P = 0.004) were lower, but acceptable, in the group of HIV-infected patients. CONCLUSIONS: In the Brazilian experience, despite somewhat inferior outcomes, kidney transplantation is an adequate therapy for selected HIV-infected recipients.

Outcomes in obese kidney transplant recipients.

BACKGROUND: Kidney transplantation (KT) in obese patients is controversial. The present study aimed to evaluate patient and graft survival and post-transplantation complications between obese and nonobese recipients. METHODS: Patients (n = 3,054) receiving a KT from 1998 to 2008 were divided according to body mass index (BMI) into 3 groups for analysis: group I: BMI <30 kg/m(2) (nonobese); group II: ≥30-34.9 kg/m(2) (class I obese); and group III: ≥35 kg/m(2) (class II and III obese). RESULTS: Mean BMIs were: group I (n = 2,822): 22.6 ± 3.3 kg/m(2); group II (n = 185): 31.9 ± 1.3 kg/m(2); and group III (n = 47): 36.8 ± 1.7 kg/m(2). There were no differences among the 3 groups in patient demographic variables regarding race, sex, or organ source. One-year (I, 98%; II, 98%; III, 95%) and 5-year (I, 90%; II, 92%; III, 89%) patient survival rates were similar among groups. Graft survival rates at 1 year were 96% for groups I and II and 91.5% for group III. Five-year graft survivals were: I, 81%; II, 96%; and III, 79%. The most common cause of graft loss was death, and the main cause of death was infection in all groups. Obese patients were more likely to experience wound dehiscence (I, 1.9%; II, 7.6%; III, 19.1%; P < .001), develop new-onset diabetes after transplantation (NODAT; I, 16.2%; II, 27%; III, 36%; P < .001), and have a prolonged length of hospital stay (I, 11.3 ± 11.4 d; II, 14.5 ± 14.3 d; III, 15.9 ± 16.7 d; P < .001). CONCLUSIONS: Obese recipients demonstrated outcomes similar to nonobese patients regarding patient and graft survival. However, they had higher rates of prolonged length of hospital stay, wound dehiscence, and NODAT.

Component analysis of hospital cost of pancreas-kidney transplant and correlations with different variables in a Brazilian hospital.

INTRODUCTION: Simultaneous pancreas-kidney transplantation is associated with a high rate of complications when it is compared with transplantation of other organs; these increased complications can result in increased financial costs of the procedure. The objective of this study was to determine operating costs and financial results of simultaneous pancreas-kidney transplantation and its different variables in a Brazilian hospital. PATIENTS AND METHODS: Between January 2008 and December 2011, the monthly costs of 105 patients were calculated. These patients were divided into 2 groups; the first consecutive 53 patients were labeled group I and the second set of 52 patients were labeled group II. The cost evaluation was made in US dollars. RESULTS: A total of 89 patients corresponded to the public health system and 16 patients to the supplementary health system. The percentage of hospital discharge was 92.4%. There was an increase in operating room costs in group II compared with group I with no statistically significant difference ($18,749.33 for group I and $17,608.26 for group II). The outcome of the operation was positive; it was greater for group II than for group I ($16,303.22 vs $3494.53). CONCLUSIONS: Simultaneous pancreas-kidney transplantation is a financially feasible procedure in Brazil, with the public health system being the main payment source.

Long-term exposure to belatacept in recipients of extended criteria donor kidneys.

Patients in the BENEFIT-EXT study received extended criteria donor kidneys and a more intensive (MI) or less intensive (LI) belatacept immunosuppression regimen, or cyclosporine A (CsA). Patients who remained on assigned therapy through year 3 were eligible to enter a long-term extension (LTE) study. Three hundred four patients entered the LTE (n = 104 MI; n = 113 LI; n = 87 CsA), and 260 continued treatment through year 5 (n = 91 MI; n = 100 LI; n = 69 CsA). Twenty patients died during the LTE (n = 5 MI; n = 9 LI; n = 6 CsA), and eight experienced graft loss (n = 2 MI; n = 1 LI; n = 5 CsA). Three patients experienced an acute rejection episode (n = 2 MI; n = 1 LI). The incidence rate of serious adverse events, viral infections and fungal infections was similar across groups during the LTE. There were four cases of posttransplant lymphoproliferative disorder (PTLD) from the beginning of the LTE to year 5 (n = 3 LI; n = 1 CsA); two of three PTLD cases in the LI group were in patients who were seronegative for Epstein-Barr virus (EBV(-)) at transplantation. Mean ± SD calculated GFR at year 5 was 55.9 ± 17.5 (MI), 59.0 ± 29.1 (LI) and 44.6 ± 16.4 (CsA) mL/min/1.73 m(2) . Continued treatment with belatacept was associated with a consistent safety profile and sustained improvement in renal function versus CsA over time.

Safety profile comparing azathioprine and mycophenolate in kidney transplant recipients receiving tacrolimus and corticosteroids.

BACKGROUND: Debate is increasing on whether mycophenolic acid (MPA) provides survival benefits comparable to azathioprine (AZA) after renal transplantation. METHODS: This retrospective cohort study compared safety and efficacy of AZA (n = 662) vs. MPA (n = 267) in low-immunologic-risk kidney transplant recipients (KTR) receiving tacrolimus (TAC) and steroids between 1998 and 2007. Primary outcomes were treatment discontinuation and infection. Secondary endpoints included survival free from biopsy-proven acute rejection, graft loss, death, and renal function. RESULTS: The 5-year survival free of treatment discontinuation was higher in the MPA compared to the AZA group (74.1% vs. 60.3%, P < 0.001). MPA was discontinued exclusively because of adverse events (16.4%), while AZA was discontinued primarily for lack of efficacy (21.2%). In univariable analysis, MPA was associated with higher incidence of total (561.5 vs. 667.5 episodes/1000 person-year, P < 0.001), bacterial (167 vs. 158 episodes/1000 person-years, P = 0.001), and viral infections (83.2 vs. 100.4 episodes/1000 person-years, P = 0.001), but this association was not confirmed in multivariable analysis. Over 29% of viral infections in the AZA group occurred after conversion to MPA. A high incidence of tuberculosis was observed (2.9 episodes/1000 person-years) with a higher incidence (but not a statistically significant difference) in the AZA group. No significant differences were found in patient survival (90% vs. 89%, P = 0.78) or graft survival (81% vs. 77.7%, P = 0.08), but infection accounted for >50% of all deaths. CONCLUSION: The type of antimetabolite, AZA or MPA, was not independently associated with any safety or efficacy outcome 5 years after transplantation, suggesting that AZA is still a viable option for low-risk KTR receiving TAC and steroids.

Lipid profile changes during the first year after kidney transplantation: risk factors and influence of the immunosuppressive drug regimen.

AIM: This study analyzed the incidence, time course, and risk factors associated with dyslipidemia during the first year after kidney transplantation among patients receiving various immunosuppressive regimens. METHODS: The analysis included 474 kidney transplant recipients receiving cyclosporine (CSA) combined with sirolimus (SRL; n=137) or mycophenolate (MMF, n=58) or everolimus (EVR, n=47); or SRL combined with MMF (n=32); or tacrolimus (TAC) combined with SRL (n=86) or MMF (n=114). All patients received prednisone. We evaluated the influence of demographic features, clinical outcomes, and statin use on lipid profiles during the first year after transplantation. total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (hdl-C), low-density lipoprotein cholesterol (ldl-C), non-HDL-C, TC:HDL-C, LDL-C:HDL-C, TG:HDL-C. RESULTS: Lipid profiles were within the recommended ranges in 28% of patients pretransplantation and in 10% at 1 year; 27% of them received statins. At 1 year, LDL-C<100 mg/dL was observed in 31.8% of patients but more than 35% of these patients still showed other lipid fractions or ratios outside recommended target concentrations. Among all patients with LDL-C>100 mg/dL, almost 70% to 80% had other lipid fractions or ratios within target ranges. A logistic regression analysis showed age, gender, time on dialysis, diabetes, type of calcineurin inhibitor (CSA vs TAC), adjunctive therapy (SRL/EVR vs MMF) and prednisone dose to be associated with dyslipidemia. CONCLUSION: Dyslipidemia is frequent at 1 year after transplantation. The lack of agreement among changes observed in lipid fractions and ratios suggests that more studies are necessary to guide therapy besides targeting LDL-C concentrations as recommended by current guidelines.

Late presentation of Alport posttransplantation anti-glomerular basement membrane disease.

We describe a female patient with Alport disease who developed antiglomerular basement membrane nephritis late after kidney transplantation during the treatment of an acute bacterial pyelonephritis and discuss the potential role of the infection as a trigger for the development of this nephritis.

The emerging role of Brazil in clinical trial conduct for transplantation.

Brazil is a country with over 190 000 000 inhabitants and a health system composed of a large public, government managed system. Between 1999 and 2010 the number of deceased donors increased by 161%, from 3.8 to 9.9 pmp, and the number of solid organ transplants increased by 121%, from 2891 to 6402. This growth was a consequence of the creation of a well-organized national transplant program. Government funding, decentralization and educational investment in transplant coordinators and related professional were decisive. In 2009 Brazil was the second largest country in the absolute number of kidney transplants (n = 4259). There are significant region disparities in performance which are mainly due to the development status. Improvements in transplant and research regulations resulted in an increasing participation of Brazilian transplant centers in multicenter trials, reaching over 44 studies during the last 11 years. Brazilian centers have been involved in clinical trials using everolimus, sirolimus, fingolimod, mycophenolate mofetyl, mycophenolate sodium, tacrolimus modified-release, sotrastaurin, belatacept, JAK3 inhibitor CP690,550 and valganciclovir. The still increasing number of transplants performed every year along with more efficient regulatory and sanitary analysis, organized clinical research programs and reduction in region performance disparities will eventually increase even more the participation of Brazil in trials worldwide.

Delayed kidney allograft function after simultaneous pancreas-kidney transplantation.

BACKGROUND: Simultaneous pancreas-kidney transplantation (SPKT) is one of the treatments for insulin-dependent chronic renal failure patients. METHODS: One-year patient and kidney allograft survival rates of 150 patients undergoing SPKT were subjected to Cox regression and Kaplan-Meier analyses. Uni- and multivariate methods identified risk factors involved in allograft and patient survival. RESULTS: One-year patient and kidney allograft survival rates were 82% and 80%, respectively. Delayed graft function (DGF) (P = .001; hazard ratio [HR]5.41) and acute kidney rejection episodes (P = .016; HR 3.36) were related to 1 year patient survival as well as intra-abdominal infection (IAI) rates. (IAI). One-year kidney allograft survival was related to DGF (P = .013; odds ratio [OR] 3.39), acute rejection (P = .001; OR 4.74), and IAI (P = .003, OR 6.29). DGF was related to a time on dialysis >27 months (P = .046; OR 2.59), cold kidney ischemia time >14 hours (P = .027; OR 2.94), donor age >25 years (P = .03; OR 2.82), and donor serum sodium concentration >155 mEq/L (P < .0001; OR 1.09). Female kidney to male recipient in 17% of the cases did not increase the risk of DGF. We observed an important correlation between donor serum sodium and creatinine (P < .0001), which suggested undertreatment of diabetes insipidus secondary to brain death. CONCLUSIONS: DGF, acute rejection, and IAI were the main determinants of survival after SPKT. Improving the care of deceased donors may reduce DGF occurrence.

Comparison of the safety and efficacy of cyclosporine minimization versus cyclosporine elimination in de novo renal allograft patients receiving sirolimus.

The safety and efficacy of concentration-controlled use of sirolimus (SRL) and cyclosporine (CsA) followed by CsA minimization (CsAm) or elimination (CsAe) beginning at week 13 was compared in a phase 4, open-label, randomized (1:1) trial of renal transplant recipients enrolled between March 2004 and November 2005. The primary endpoint was renal function, measured at 12 months using the Nankivell formula, in patients remaining on therapy. Though a total enrollment of 140 patients in each group was planned to provide an 80% power to detect a difference in means, only 207 subjects were enrolled in this study. Demographic characteristics were similar between groups, with 98.1% recipients of first grafts, 69.1% from living donors, and 7.2% diabetics. At 12 months, there were no differences in renal function (61.08 vs 65.24 mL/min, P = .132); incidence of biopsy-confirmed acute rejection (14.3% vs 22.5%, P = .152); and patient (89.5% vs 92.2%, P = .632), graft (87.6% vs 88.2%, P = .999), and death-censored graft (98.1% vs 94.1%, P = .166) survivals between CsAm and CsAe groups, respectively. There were no differences in the overall rate of study-drug discontinuation (32.4% vs 36.3%, P = .562) but more patients discontinued because of lack of efficacy/graft loss in the CsAe group (4.8% vs 14.7%, P = .018). This study was underpowered to demonstrate the superiority of one regimen over the other. In summary, SRL immunotherapy combined with CsA minimization or elimination showed comparative safety and efficacy. Both regimens offer potential treatment options for de novo renal allograft recipients.

What is the impact of surgical site infection on graft function in kidney transplant recipients?

The impact of surgical site infections (SSIs) on graft function in kidney transplant recipients is controversial. We conducted a matched case-control study (1:1 ratio) between April 2001 and December 2004 in a Brazilian cohort of kidney transplant recipients. The epidemiological and clinical characteristics of SSIs were described based on chart review. The impact on graft function was assessed by comparing serum creatinine measurements and creatinine clearance up to 18 months after transplantation with analysis of variance model. Among 1939 kidney transplants, 120 patients with 145 SSIs were enrolled. Most wound infections were superficial (73.1%). The mortality rate was 0.8%. No impact on graft function was detected. In conclusion, accurate identification of SSIs may have resulted in shorter hospitalization periods, but they had no impact on graft function up to 18 months post transplantation.

Clinical implications of initial renal function after deceased donor transplant.

The aim of this study was to investigate whether slow graft function (SGF) after transplantation of deceased-donor kidneys affected the prevalence of anemia or the glomerular filtration rate (GFR). We retrospectively evaluated the records of 534 kidney transplant patients who were classified based on their initial renal function, namely, immediate graft function (IGF), slow graft function (SGF), or delayed graft function (DGF). Among the 534 kidney transplant patients studied, the occurrences of each condition were IGF 104, SGF 133, and DGF 297. Six months after transplantation, a greater percentage of DGF patients were anemic compared with the others (P = .028). However, at 12 months after transplantation, SGF patients showed more anemia than the IGF group. DGF and SGF patients displayed similar GFR values at 18 and 24 months after transplantation. However, IGF patients displayed higher GFRs, even when subjects who experienced acute rejection episodes were censored (P = .004). The incidence of acute rejection episodes was similar among SGF and DGF patients. Patients displaying SGF after deceased-donor transplantation showed a greater tendency to be anemic than those displaying IGF. This study also suggested that SGF patients were at risk for acute rejection episodes and/or significantly reduced kidney function as measured by GFR.

Infectious complications after deceased kidney donor transplantation.

BACKGROUND: Despite improvements in immunosuppressive therapy, infections remain a complication of renal transplantation that is associated with increased morbidity and graft rejection. The aim of this study was to evaluate the relationship between initial renal function after deceased donor transplantation and viral infections. METHODS: We included patients 18 years and older who received a deceased donor transplantation between January 1995 and December 2004. They were divided into 2 groups: cases from 1994 to 1999, versus from 2000 to 2004. Initial renal function was classified as immediate (IGF), slow (SGF), or delayed (DGF). Infections were classified according to Centers for Disease Control and prevention standards. RESULTS: Among 534 patients, SGF and DGF patients who underwent immunosuppression between 2000 and 2004 show a higher infection rate than IGF patients (P = .005). SGF patients showed a higher incidence of tissue-invasive cytomegalovirus disease (P < .001). Second episodes of viral infections were more common among all patients in this period. However, DGF patients were more susceptible to second episodes of viral infection. In the first group, OKT3 use (P = .013) and donor age (P = .012) were the major risk factors associated with viral infections whereas in the second group, thymoglobulin use (P = .002), acute rejection episode (P = .003), and anemia (P = .044) were the risk factors for viral infection. CONCLUSION: Initial renal function after deceased donor transplantation was correlated with viral infection. DGF patients had a higher risk for second infection episodes. SGF patients had a higher risk for tissue-invasive cytomegalovirus infection.

Extreme subcutaneous, intramuscular and inhaled insulin resistance treated by pancreas transplantation alone.

Diabetes mellitus with resistance to insulin administered subcutaneously or intramuscularly (DRIASM) is a rare syndrome and is usually treated with continuous intravenous insulin infusion. We present here two cases of DRIASM in 16 and 18 years female patients that were submitted to pancreas transplantation alone (PTA). Both were diagnosed with type 1 diabetes as young children and had labile glycemic control with recurrent episodes of diabetic ketoacidosis. They had prolonged periods of hospitalization and complications related to their central venous access. Exocrine and endocrine drainages were in the bladder and systemic, respectively. Both presented immediate graft function. In patient 1, enteric conversion was necessary due to reflux pancreatitis. Patient 2 developed mild postoperative hyperglycemia in spite of having normal pancreas allograft biopsy and that was attributed to her immunosuppressive regimen. Patient 1 died 9 months after PTA from septic shock related to pneumonia. In 8 months of follow-up, Patient 2 presented optimal glycemic control without the use of antidiabetic agents. In conclusion, PTA may be an alternative treatment for DRIASM patients.

Mycophenolate mofetil versus enteric-coated mycophenolate sodium after simultaneous pancreas-kidney transplantation.

INTRODUCTION: Adverse gastrointestinal events are frequent after mycophenolate use. The objectives of the present study were to report the incidence of acute noninfectious diarrhea, to determine the risk factors, and to compare the severity of reactions between mycophenolate mofetil (MMF) and enteric-coated mycophenolate sodium (EC-MPS) after simultaneous pancreas kidney transplantation (SPKT). METHODS: We included 165 SPKT patients from December 2000 to May 2007. Uni- and multivariate analyses were performed, using acute noninfectious diarrhea as the dependent variable. P < .05 was considered significant. RESULTS: Mean age and duration of dialysis and of diabetes were 34.9 +/- 8.2 years, 27.3 +/- 18.3 months, and 21.9 +/- 16.2 years, respectively. Sixty-three percent used MMF, 36.4% used EC-MPS, and 0.6% used azathioprine. Multivariate analysis showed that the duration of diabetes (P = .049, confidence interval [CI] 1.0- 1.13) and MMF use (P = .013, 95% CI 0.2-0.82) were the main determinants of acute diarrhea after SPKT. MMF dose reduction (79.2% vs 62.3%, P = .024) and severity of diarrhea associated with orthostatic hypotension were more pronounced among MMF than EC-MPS patients (42.4% vs 15.1%, P = .001). There was no difference between MMF and EC-MPS after dose reduction in relation to the occurrence of acute kidney rejection (30.8% vs 26.7%, P = .53). CONCLUSIONS: Acute noninfectious diarrhea after SPKT was related to the duration of diabetes and to prescription of MMF. Preferential use of EC-MPS was associated with a lower necessity of dose reduction and less severe episodes of acute diarrhea compared with MMF, although dose reduction was equally associated with acute episodes of kidney rejection.

Risk factors associated with graft loss and patient survival after kidney transplantation.

OBJECTIVE: To evaluate the influence of traditional risk factors on major kidney transplantation outcome. PATIENTS AND METHODS: Data from kidney transplantation procedures performed between 2003 and 2006 were retrospectively analyzed for the influence of traditional risk factors on transplantation outcome. Of 2364 transplants, 67% were from living donors, 27% were from donors who met standard criteria, and 6% were from donor who met expanded criteria. Two hundred thirty-nine procedures (10%) were performed in pediatric patients. Immunosuppression was selected on the basis of subgroup population. RESULTS: At 1 year posttransplantation, cumulative freedom from a treated acute rejection episode (ARE) was 76.7%, with no difference between black vs nonblack recipients (75.0% vs 73.4%; P = .79). At 2 years, survival for patients (95.3% vs 88.3% vs 82.1%; P < .001) and grafts 92.3% vs 80.3% vs 70.9%; P < .001) was better in recipients of living donor grafts compared with donors who met standard or expanded criteria, respectively. Moreover, graft survival was poorer in black vs nonblack patients (83.6% vs 88.7%; P < .05) because of high mortality (13% vs 7%; P<.001). Risk factors associated with death included cadaveric donor organ (odds ratio [OR], 2.4) and black race (OR, 1.8), and risk factors associated with graft loss included cadaveric donor organ (OR, 2.1), extended-criteria criteria donor organ (OR, 2.0), delayed graft function (OR, 1.8), and any ARE (OR, 3.5). At 6 months posttransplantation, risk factors associated with death included cadaveric donor organ (OR, 2.5) or ARE (OR, 2.4), and risk factors associated with graft loss included cadaveric donor organ (OR, 2.0), extended-criteria donor organ (OR, 2.6), ARE (OR, 9.5), and impaired graft function (creatinine concentration >1.5 mg/dL; OR, 2.1). CONCLUSION: Traditional risk factors are still associated with transplantation outcome. Poorer graft survival in black vs nonblack recipients was due to higher mortality rather than graft loss.

Clinical impact of polymorphisms of transport proteins and enzymes involved in the metabolism of immunosuppressive drugs.

Individualization of immunosuppressive therapy after solid organ transplantation is a goal that has been pursued for a long time. Nevertheless, in clinical practice, we are still stratifying patients in subgroups in which risk is assessed using demographic information and population analysis. Then, a combination of immunosuppressive drugs is chosen and doses are individualized to compensate for intra- and interindividual variabilities in drug pharmacokinetics, to obtain similar plasma/blood concentrations that are believed to be therapeutic, again based on data derived from population analysis. One step further in this strategy is to recognize, before initiation of immunotherapy, those patients at higher risk to be either under- or overexposed to currently used immunosuppressive drugs. Several studies have been undertaken to correlate single nucleotide polymorphisms in genes encoding transport proteins and metabolizing enzymes involved in the disposition of immunosuppressive drugs. Overall, the results from these studies have been mixed. The causes of these sometimes conflicting results include methodologic, genetic, or nongenetic factors. The degree of linkage disequilibrium, the measure of nonrandom associations between polymorphisms at different loci, not necessarily on the same chromosome, is perhaps the main genetic factor. The influence of the environment, physiology (such as kidney and liver functions), disease state, use of multidrug regimens, and inherent drug-to-drug interactions are present nongenetic factors. Moreover, it is also important to increase our knowledge of the genetic factors involved in the variabilities observed in drug responses of pharmacodynamics. True individualized therapy, with the ability to improve health outcomes of each transplant recipient, will depend on our knowledge of the genetic factors involved in immunological response and drug pharmacokinetics and pharmacodynamics.