Fatigue effects in daily life activities of kidney transplant recipients.

After undergoing kidney transplantation, some patients still face one symptom that continues after the dialysis sessions: fatigue (physical and mental tiredness that does not get better after resting). Fatigue effects in the everyday lives of kidney transplant patients can be beneficially modified early by changing this scenario. This is a quantitative study about the intensity and impacts of fatigue in kidney transplant patients admitted to the Hypertension and Kidney Hospital from October 2011 to March 2012. The fatigue pictogram was used to evaluate the level of fatigue interference in the daily life activities of kidney transplant patients. The sample consists of 39 patients, and was developed in 2 phases: data collection and attendance after and before the transplantation until hospital discharge. Descriptive statistical analyses were used. In the group at issue, we have noticed the following profile of the sample: 84.3% of transplantations with live donors, most were men, average age 36.5 years old, average hospitalization time 11.1 days, average time of renal failure 66.4 months, systemic arterial hypertension prevalence 66.7%, and the prevalence of at least 1.8 diseases in each individual. The self-referred causes of chronic renal failure were uncontrolled systemic arterial hypertension, glomerulonephritis, and overuse of anti-inflammatory drugs, among others. The study shows that fatigue is directly related to the level of activities of daily living, causing less ability to perform activities in the higher level of fatigue, which is in the immediate postoperative period and only settling fully on the 9th postoperative day.

Planned randomized conversion from tacrolimus to sirolimus-based immunosuppressive regimen in de novo kidney transplant recipients.

Planned conversion from tacrolimus to sirolimus was evaluated in de novo kidney transplant recipients. In this multicenter, randomized, open-label study, 297 patients were initially treated with tacrolimus, mycophenolate sodium and prednisone. Of the 283 patients reaching 3 months, 97 were converted to sirolimus (SRL), 107 were maintained on tacrolimus (TAC) and 79 were patients receiving TAC without criteria to undergo intervention at month 3 (TACex). The primary objective was to show superior estimated glomerular filtration rate (eGFR) in the SRL group at month 24. Of the 258 patients who completed 24 months, 91 (94%) were in the SRL group, 101 (94%) in the TAC group and 66 (84%) in the TACex group. In the intention-to-treat population there were no differences in eGFR (66.2 ± 25.3 vs. 70.7 ± 25.1, p = 0.817) or in the severity of chronic sclerosing lesions scores in 24-month protocol biopsies. Higher mean urinary protein-to-creatinine ratio (0.36 ± 0.69 vs. 0.15 ± 0.53, p = 0.03) and higher incidence of treated acute rejection between months 3-24 (13.4% vs. 4.7%, p = 0.047) were observed in SRL compared to TAC group. In this population planned conversion from TAC to SRL 3 months after kidney transplantation was not associated with improved renal function at 24 months.

Cardiovascular disease in early kidney transplantation: comparison between living and deceased donor recipients.

BACKGROUND: Cardiovascular disease (CVD) mortality is extremely high among kidney transplant recipients (KTRs), particularly in the first months after transplantation. Few data are available comparing the cardiovascular profile between KTRs from living versus deceased donors. OBJECTIVES AND METHODS: The aim of the present study was to evaluate the prevalence of CVD in the first 2 months following transplantation, among 120 KTRs of living versus deceased donor organs. RESULTS: Left ventricular hypertrophy was observed in 65% of patients, coronary artery calcification in 30%, and cardiac arrhythmias in 46%. CVD was more prevalent among KTRs from deceased versus living donors: ventricular hypertrophy 87% versus 59% (P = .008); coronary artery calcification 42% versus 24% (P = .04); and cardiac arrhythmias 59% versus 39% (P = .06). Multiple logistic regression analysis adjusted for age and dialysis vintage, showed graft donor to not be associated with the prevalence of any CVD (ß coefficient 0.912, 95% confidence interval 0.276-3.012, P = .88). CONCLUSION: In conclusion, the present study demonstrated an elevated prevalence of CVD among KTRs. Patient characteristics, mainly longer length on dialysis seemed to contribute to a greater prevalence of cardiovascular complications among KTRs from deceased compared with living donors on univariate but not multivariate analysis.

Multivariate analysis of risk factors for early loss of pancreas grafts among simultaneous pancreas-kidney transplants.

UNLABELLED: To evaluate the risk factors for pancreas graft loss within 3 months postoperatively among 170 simultaneous pancreas-kidney transplantation (SPKT) we examined 38 variables. METHODS: Twenty-two variables were related to recipients; 12 to donors and 4 to the surgical procedure. In addition the latest follow-up dates as well as the transplant and/or death dates. Independent variables were examined with reference to the dependent pancreatic loss variable, excluding losses owing to deaths. Variables with statistical significance were analyzed to predict early graft loss. RESULTS: Univariate analyses determined the following significant variables: kidney cold ischemia time, older donors, non-white donors, death cause related to vascular disease, wound infection, and length of extended hospitalization. However, multivariate analysis showed that only donor age and kidney cold ischemia time were significant predictors for early pancreatic graft loss. CONCLUSION: Donor age and kidney cold ischemia time were independently related to pancreatic loss after SPKT within 3 months posttransplantation.

Cystatin C and renal function in pediatric kidney transplant recipients

In clinical practice, the glomerular filtration rate (GFR) is often determined with serum creatinine. However, studies have shown cystatin C to be a better parameter for the diagnosis of impaired renal function. We compared GFR estimated by plasma cystatin C with GFR estimated by serum creatinine in a sample of 50 pediatric renal transplant recipients and 24 healthy children. The correlation between GFR estimated by serum creatinine and by cystatin C was significant (r = 0.75; P < 0.001, Person’s correlation); however, in pediatric kidney transplant recipients, the GFR was 6.7 mL/min lower when determined using cystatin C rather than serum creatinine. Moreover, using GFR estimated by cystatin C we found that 42 percent of the pediatric kidney transplant recipients had an estimated GFR <60 mL·min-1·1.73 (m²)-1, whereas when GFR was estimated by the serum creatinine formula only 16 percent of the children had values below this cutoff point indicative of chronic kidney disease (P < 0.001). We conclude that, in pediatric kidney transplant recipients, estimation of GFR yields lower values when cystatin C is used rather than serum creatinine.

Cystatin C and renal function in pediatric kidney transplant recipients.

In clinical practice, the glomerular filtration rate (GFR) is often determined with serum creatinine. However, studies have shown cystatin C to be a better parameter for the diagnosis of impaired renal function. We compared GFR estimated by plasma cystatin C with GFR estimated by serum creatinine in a sample of 50 pediatric renal transplant recipients and 24 healthy children. The correlation between GFR estimated by serum creatinine and by cystatin C was significant (r = 0.75; P < 0.001, Person's correlation); however, in pediatric kidney transplant recipients, the GFR was 6.7 mL/min lower when determined using cystatin C rather than serum creatinine. Moreover, using GFR estimated by cystatin C we found that 42% of the pediatric kidney transplant recipients had an estimated GFR <60 mL.min-1.1.73 (m(2))-1, whereas when GFR was estimated by the serum creatinine formula only 16% of the children had values below this cutoff point indicative of chronic kidney disease (P < 0.001). We conclude that, in pediatric kidney transplant recipients, estimation of GFR yields lower values when cystatin C is used rather than serum creatinine.

Incidence and risk factors for surgical site infection after simultaneous pancreas-kidney transplantation.

A simultaneous pancreas-kidney transplantation (SPKT) is the best treatment option for type I diabetic patients with advanced chronic renal failure. Infectious complications affect 7-50% of the patients receiving this procedure. We conducted a nested case-control study to assess the risk factors for surgical site infection (SSI) in patients receiving SPKT at our centre between 2000 and 2006. Of the 119 evaluated transplant recipients, 55 (46.2%) developed SSIs and the 30 day mortality was 11.8%. Gram-negative organisms were the predominant organisms isolated from SSIs. After multivariate logistic regression, the variables independently associated with SSI were: acute tubular necrosis, post-transplant fistula and graft rejection. This study demonstrated a high incidence of SSI in this patient cohort and variables related to the surgical procedure were closely associated with the development of SSI.

FTY720 prevents renal T-cell infiltration after ischemia/reperfusion injury.

Ischemia/reperfusion (I/R) injury, a common early feature in renal transplantation, results from both free radical species generation and local inflammatory responses that attract different types of cells. The interaction with infiltrating leukocytes could promote damage and death of resident renal cells contributing to worsening of renal function. It has been shown that depletion of host T cells protects against kidney damage after I/R injury, although the mechanism is not fully understood. FTY720, a synthetic analog of a natural product extracted from Isaria sincclairii has shown modulatory properties in experimental models of autoimmune disease, transplantation, and I/R injury. FTY720 alters lymphocyte responses to chemokine homing signals, thereby decreasing the number of lymphocytes in inflammatory sites. We evaluated renal function in mice at 3, 5, and 7 days after I/R injury in the presence or absence of FTY720 treatment. FTY720 treatment promoted earlier recovery of renal function associated with a lower number of renal-infiltrating lymphocytes. These findings confirm previous results showing a protective effect of FTY720 in I/R injury models.

Sequential cytomegalovirus antigenemia monitoring in kidney transplant patients treated with antilymphocyte antibodies.

BACKGROUND: Antilymphocyte antibodies (ALA) use is related to disseminated cytomegalovirus (CMV) disease after kidney transplantation. Strict surveillance of CMV infection, preemptive antiviral treatment or concomitant ganciclovir and ALA use are proposed as an attempt to prevent related clinical complications. Our objective was to describe the pattern of CMV infection, based on sequential antigenemia detection, after ALA treatment. PATIENTS AND METHODS: Thirty renal transplant patients were prospectively screened for CMV infection after ALA treatment. CMV antigenemia (pp65 antigen detection) was monitored twice a week in the first month and weekly until 60 days after the beginning of ALA therapy. Any positive value of antigenemia was considered CMV infection. RESULTS: Twenty-eight (93.3%) patients were CMV positive (IgG) before transplantation. The mean duration of ALA treatment was 12.1+/-2.4 days. Positive antigenemia was detected in 24 (80%) patients, a mean of 52.5+/-15 days after transplant and 44.7+/-14 days after the beginning of ALA treatment. The median antigenemia count was 7 positive cells/300,000 neutrophils (range: 1-227). Antigenemia preceded clinical symptoms by 5.8 days (0-28 days). Eighteen (75%) of 24 positive patients received ganciclovir treatment: 8 patients (26.7%) for viral syndrome, 2 patients (33.3%) for invasive disease, and 8 patients (26.7%) as part of preemptive therapy, asymptomatic with high antigenemia values. Six pp65-positive patients with low counts were followed up until a negative result and remained asymptomatic without any specific treatment. CONCLUSION: CMV infection was frequent after ALA treatment in this group and generally occurred late after completion of treatment. Antigenemia was a reliable tool to guide preemptive treatment in these patients, and such strategy is an alternative option compared to the prophylactic use of ganciclovir with ALA treatment.

Prevalence of previous hepatitis A virus infection in renal transplant patients with hepatitis C: evidence of persistent anti-hepatitis A virus immune response.

Data concerning the prevalence of hepatitis A virus (HAV) infection among kidney transplant recipients are scarce. There is little information concerning natural immunity acquired after acute HAV infection. In most renal transplant recipients, anti-HAV antibodies are not detectable after vaccination; it is reasonable to suppose that immunosuppressive therapy interferes with the immunity. The objective of this study was to evaluate, in an endemic area, the prevalence of anti-HAV immunoglobulin (Ig)G in renal transplant recipients with chronic hepatitis C virus (HCV) infection. The prevalence of anti-HAV IgG was assessed in 40 HCV-positive renal transplant recipients. This group showed a 90% prevalence of previous HAV infection. These findings suggest that in an endemic area, the prevalence of previous HAV infection is high, even among immunosuppressed patients. HAV antibodies acquired after natural infection are detectable even after the onset of immunosuppressive therapy. These data should be considered when renal transplant recipients are considered for HAV vaccination. Prevaccination screening of renal transplant recipients must follow the same guidelines as those for immunocompetent subjects.

Do we need living unrelated organ donation in Brazil?

The remarkable success achieved by organ transplantation has also engendered the major problem of organ shortage. As a consequence, the use of living unrelated donors (LURD) has been proposed as an ethically justifiable alternative for developed nations to minimize their waiting lists for organ transplantation (OTx). This change in attitude has caused an ethical dilemma for developing countries like Brazil, which is struggling to increase the cadaver donor pool. Due to a huge socioeconomic gap of values and needs among nations, the incentive to use LURD in developed countries may not only produce a disincentive to cadaver organ donation but also stimulate organ trade in developing countries. In this paper we aimed to show that in Brazil, we do not need to use LURD because we have not optimized our cadaver donor pool. The exploitation of LURD might be a good option for developed countries, but it is not useful for developing countries. The Transplantation Society urgently needs to solve and clarify this problem by establishing basic ethical and justice principles that can serve as a guide for every country, throughout the entire process required, to achieve an adequate pool of cadaver donors.

Expanding criteria for the use of living donors: what are the limits?

The cadaver organ shortage has pushed the transplant community to extend the boundaries beyond the traditional criteria used for living donor transplantation. This new liberal policy involves: (1) the type of donor, such as emotionally related individuals, the direct or indirect interchange of donors, anonymous as well as rewarded donation; (2) challenging immunological criteria, using incompatible ABO blood types and or transplantation across a positive cross-match; (3) relaxing clinical criteria related to elderly, hypertensive, or obese donors, or patients with nephrolithiasis, fibromuscular renal artery disease, hematuria, or renal cell carcinomas. However, these practices may be dangerous. They must be clearly validated to promote a liberal policy of donor acceptance since it may carry a risk for both the donor and the recipient as well as for society. It is crucial to ensure the physical integrity of the donor as well as to provide guarantees, for instance a 1-year policy of life insurance, an indefinite long-term medical follow-up and the assurance of going to the top of the waiting list if the donor becomes uremic in the future.

FTY720 impairs necrosis development after ischemia-reperfusion injury.

Ischemia-reperfusion (IR) injury is a common early feature that contributes to graft damage by impairing resident cell function. Our previous results showed that IR injury impaired renal function, by causing extensive tubular necrosis and increasing MHC class II and ICAM-1 molecule expression by mesangial cells (MC). MCs are likely candidates to come into close contact with immune cells such as monocytes or lymphocytes. It has been suggested that under inflammatory circumstances, there is increased MC expression of MHC class II, of adhesion molecules (such as ICAM-1), of cytokines receptors, and of molecules associated with cellular death (apoptosis). The immunosuppressive properties of FTY720 have been shown in clinical and experimental situations. It has also been shown to be protective against IR injury in rats. We sought to evaluate the role of FTY720 in a murine IR model by measuring renal function, tubular necrosis, and surface molecule expression by cultured mesangial cells. Intravenous administration of FTY720 (1 mg/kg) immediately before IR induction did not improve the short-term (24 hours) outcome of renal function or reduced MHC class II and ICAM-1 surface molecule expression. However, there was a decreased percentage of tubular necrosis in mice treated with FTY720 (51.3% +/- 1.6%) compared with vehicle-treated mice (66% +/- 5.5%). These results suggest a protective role of FTY720 in an IR injury model. More studies are required to identify the mechanisms involved in the protective activity of FTY720 in the IR injury model.

Simultaneous pancreas-kidney transplantation: infectious complications and microbiological aspects.

OBJECTIVE: The purpose of this study was to describe the clinical and microbiological characteristics of the infectious complications among simultaneous pancreas-kidney transplantations (SPKT). MATERIALS AND METHODS: Among the first 45 SPKT the mean age was 34 years (range, 21 to 49) and the mean duration of follow-up 13 months (range, 2 to 27 months). RESULTS: Twenty-three patients (51%) presented at least one to three episodes (1.7 mean) of infectious complications that needed hospitalization. The etiology of the infections included 71% bacterial (44% gram-negative rods and 27% gram-positive cocci), 16% viral (12% from CMV and 4% from Herpes sp) and 13% fungal (8% by Candida sp and 4% by others fungus). Wound and urinary infections were most frequent, occurring in 22% and 28% of the patients, respectively. All patients who were submitted to vesical drainage developed infections in contrast a rate of only 44% among patients undergoing enteric drainage. CONCLUSION: Infectious complications are the main cause of morbidity and mortality following simultaneous pancreas-kidney transplantation, especially with vesical drainage. The use of enteric drainage combined with administration of broad spectrum prophylactic antibiotics is recommended.

Risk factors for the development of posttransplantation diabetes mellitus in simultaneous pancreas and kidney recipients.

We sought to determine the risk factors involved in the development of posttransplantation diabetes mellitus (PTDM) following simultaneous pancreas and kidney transplantation. Correlations were sought between tacrolimus (FK-506) levels/dose 2-hour capillary glucose (CG) and glycosylated hemoglobin (HbA(1c)), cyclosporine (CSA) levels/dose with HbA1c, 2-hour CG with prednisone dose and body mass index (BMI) and PTDM. Four patients (9.3%) developed PTDM. Three treated with FK-506 had altered 2-hour CG at 3 months after transplantation; 1 prescribed CSA displayed diabetes diagnosed after 1 year. There was no statistically significant difference among HbA(1c) values and FK-506 (P =.18) or CSA (P =.81) doses or FK-506 (P =.53) and CSA (P =.54) levels. In contrast, there was a statistically significant relationship between elevated 2-hour CG (> or =200 mg/dL) and daily prednisone dose (9.7 mg vs. 16.2 mg; P =.003). There was no correlation between 2-hour CG and FK-506 dose (P =.084) or FK-506 levels (P =.075). The greater BMI correlated with an increased risk of PTDM (21.25 +/- 3.13 kg/m(2) vs 24.67 +/- 2.38 kg/m(2); P =.034). Two-hour CG may be a useful tool to screen the diabetogenic effects of corticosteroids. A BMI increase should be discouraged due to the risk of PTDM.

FTY720 treatment prolongs skin graft survival in a completely incompatible strain combination.

FTY720 has shown potent immunomodulatory activity in a variety of animal organ transplant models. However, the in vivo immunosuppressive mechanism of FTY720 is still not fully understood. It has been suggested that the marked decrease in the number of peripheral blood lymphocytes during FTY720 administration could be responsible for its immunosuppressive effects. Our aims were: (1) to study the effects of FTY720 treatment on skin graft survival using a fully mismatched strain combination and (2) to evaluate lymphocyte numbers in different sites at 5 days after skin transplant. C57BL/6 mice and BALB/c mice were the donors and recipients respectively. BALB/c mice received FTY720 (1 mg/kg/d) orally for 4 consecutive days. Drug administration started 1 day before skin transplants. A small segment of tail skin was affixed on the right dorsal side of the mouse via sutures. The administration of FTY720 (4 mg/kg) prolonged skin graft survival from 12.6 +/- 2.2 days (no treatment) to 16.6 +/- 4.2 days. The histologic findings of rejection were similar for all groups. Five days after transplant, lymphocyte numbers were significantly increased in lymph nodes compared with nontransplanted or isogenic graft mice. FTY720 decreased lymphocyte numbers only in the spleen. In conclusion, FTY720 prolonged skin graft survival in a fully mismatched strain combination when administered for 4 days (day -1 to day +2) at a dose of 1 mg/kg/d. The decreased number of lymphocytes in the spleen suggests that the spleen may be a target of FTY720 activity, during the early posttransplant period.

The role of CD8+ T cells during allograft rejection.

Organ transplantation can be considered as replacement therapy for patients with end-stage organ failure. The percent of one-year allograft survival has increased due, among other factors, to a better understanding of the rejection process and new immunosuppressive drugs. Immunosuppressive therapy used in transplantation prevents activation and proliferation of alloreactive T lymphocytes, although not fully preventing chronic rejection. Recognition by recipient T cells of alloantigens expressed by donor tissues initiates immune destruction of allogeneic transplants. However, there is controversy concerning the relative contribution of CD4+ and CD8+ T cells to allograft rejection. Some animal models indicate that there is an absolute requirement for CD4+ T cells in allogeneic rejection, whereas in others CD4-depleted mice reject certain types of allografts. Moreover, there is evidence that CD8+ T cells are more resistant to immunotherapy and tolerance induction protocols. An intense focal infiltration of mainly CD8+CTLA4+ T lymphocytes during kidney rejection has been described in patients. This suggests that CD8+ T cells could escape from immunosuppression and participate in the rejection process. Our group is primarily interested in the immune mechanisms involved in allograft rejection. Thus, we believe that a better understanding of the role of CD8+ T cells in allograft rejection could indicate new targets for immunotherapy in transplantation. Therefore, the objective of the present review was to focus on the role of the CD8+ T cell population in the rejection of allogeneic tissue.